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Wang YC, Lin YT, Hsieh PH, Lai CW, Chen SF, Chen MH, Tung FI, Liu TY. On-site delivery of bioactive nanospheres utilizing lanthanides as crosslinkers and metastasis-inhibiting agents for breast cancer therapy. J Control Release 2025; 382:113671. [PMID: 40158810 DOI: 10.1016/j.jconrel.2025.113671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/26/2025] [Accepted: 03/27/2025] [Indexed: 04/02/2025]
Abstract
Postoperative breast cancer patients face a critical 2-3-week window during which residual tumor cells are highly prone to metastasis, yet systemic therapies are often ineffective due to impaired vascularization and limited drug transport. To address this challenge, we developed an injectable nanosphere formulation based on hyaluronic acid (HyA) crosslinked with lanthanide ions-europium (Eu) or lanthanum (La) ions-that act dually as physical crosslinkers and therapeutic agents. This dual-function design ensures structural stability without chemical crosslinkers, while actively inhibiting cancer cell migration, invasion, and colonization. The small ionic size of lanthanides facilitates deep interstitial transport, overcoming diffusion barriers in poorly perfused tissues. Upon injection, the nanospheres swell to sub-micrometer dimensions, achieving prolonged retention at the tumor site and sustained ion release for up to 21 days. In vitro and in vivo studies revealed distinct anti-metastatic profiles: HyA-Eu nanospheres effectively suppressed migration and distant metastasis, whereas HyA-La nanospheres inhibited colony formation and primary tumor growth. These results demonstrate a novel lanthanide ion-mediated strategy for post-surgical cancer therapy, integrating local retention with controlled ion release to bridge the treatment gap during recovery.
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Affiliation(s)
- Yu-Chi Wang
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Yan-Ting Lin
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Ping-Hsun Hsieh
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Chen-Wei Lai
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Shuo-Fu Chen
- Department of Heavy Particles & Radiation Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan
| | - Ming-Hong Chen
- Division of Neurosurgery, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City 220216, Taiwan; Department of Electrical Engineering, Yuan Ze University, Taoyuan City 320315, Taiwan
| | - Fu-I Tung
- Department of Orthopaedics, Yang-Ming Branch, Taipei City Hospital, Taipei 111024, Taiwan; Department of Health and Welfare, College of City Management, University of Taipei, Taipei 111036, Taiwan.
| | - Tse-Ying Liu
- Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
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2
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Farahavar G, Abolmaali SS, Biabanikhankahdani R, Tamaddon AM. Synergistic action of combining photodynamic therapy with immunotherapy for eradicating solid tumors in animal models: A systematic review. Crit Rev Oncol Hematol 2025; 209:104691. [PMID: 40058741 DOI: 10.1016/j.critrevonc.2025.104691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/25/2025] [Accepted: 03/01/2025] [Indexed: 03/24/2025] Open
Abstract
Malignancies maintain a high rate of mortality worldwide each year, requiring the development of novel therapeutic platforms. Immunotherapy approaches are considered a revolutionary treatment for overcoming malignancies. Photodynamic therapy (PDT) has attracted significant attention in various cancer types. Recent progress in cancer therapies has underscored the potential of combining PDT with immunotherapy. This approach can improve therapeutic outcomes by directly eliminating tumor cells and boosting immune responses for sustained anti-tumor effects in the whole body. This study aims to determine the relative efficacy of combining PDT with immunotherapy compared to PDT alone. Following the PRISMA guidance, an extensive literature review was conducted utilizing Scopus, Web of Science, and PubMed to identify high-quality preclinical studies exploring various aspects of PDT combined with immunotherapy. The adopted PICO framework included studies with rigorous experimental designs and relevant outcomes. The present review reveals the characteristics of tumor models, delivery systems, photosensitizers, and immunotherapy approaches. Key findings indicate that the combined PDT-immunotherapy approach shows promise in treating multiple tumors according to their size, therapeutic biomarkers, and inhibition of distant tumors. Finally, this integrated therapeutic strategy holds significant promise for advancing cancer treatment paradigms by potentiating each treatment efficacy; however, its clinical utility requires careful consideration of the associated challenges.
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Affiliation(s)
- Ghazal Farahavar
- Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Samira Sadat Abolmaali
- Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Nanotechnology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Roya Biabanikhankahdani
- Department of Basic Sciences, College of Dentistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
| | - Ali Mohammad Tamaddon
- Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Nanotechnology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutics Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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3
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Zhou JJ, Feng YC, Zhao ML, Guo Q, Zhao XB. Nanotechnology-driven strategies in postoperative cancer treatment: innovations in drug delivery systems. Front Pharmacol 2025; 16:1586948. [PMID: 40371327 PMCID: PMC12075547 DOI: 10.3389/fphar.2025.1586948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Accepted: 04/23/2025] [Indexed: 05/16/2025] Open
Abstract
Cancer remains a global health challenge, and this challenge comes with a significant burden. Current treatment modalities, such as surgery, chemotherapy, and radiotherapy, have their limitations. The emergence of nanomedicines presents a new frontier in postoperative cancer treatment, offering potential to inhibit tumor recurrence and manage postoperative complications. This review deeply explores the application and potential of nanomedicines in the treatment of cancer after surgery. In particular, it focuses on local drug delivery systems (LDDS), which consist of in situ injection, implantation, and spraying. LDDS can provide targeted drug delivery and controlled release, which enhancing therapeutic efficacy. At the same time, it minimizes damage to healthy tissues and reduces systemic side effects. The nanostructures of these systems are unique. They facilitate the sustained release of drugs, prolong the effects of treatment, and decrease the frequency of dosing. This is especially beneficial in the postoperative period. Despite their potential, nanomedicines have limitations. These include high production costs, concerns regarding long-term toxicity, and complex regulatory approval processes. This paper aims to analyze several aspects. These include the advantages of nanomedicines, their drug delivery systems, how they combine with multiple treatment methods, and the associated challenges. Future research should focus on certain issues. These issues are stability, tumor specificity, and clinical translation. By addressing these, the delivery methods can be optimized and their therapeutic efficacy enhanced. With the advancements in materials science and biomedical engineering, the future design of LDDS is set to become more intelligent and personalized. It will cater to the diverse needs of clinical treatment and offer hope for better outcomes in cancer patients after surgery.
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Affiliation(s)
- Jun-Jie Zhou
- The Stomatological Hospital, Anyang Sixth People’s Hospital, Anyang, China
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4
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Li L, Chen M, Reis RL, Kundu SC, Xiao B, Shi X. Advancements of nanoscale drug formulations for combination treatment of colorectal cancer. Int J Pharm 2025; 674:125508. [PMID: 40132771 DOI: 10.1016/j.ijpharm.2025.125508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/10/2025] [Accepted: 03/21/2025] [Indexed: 03/27/2025]
Abstract
Combination chemotherapy is widely utilized in treating colorectal cancer (CRC), particularly for patients who are ineligible for surgery or those with metastatic CRC (mCRC). While this therapeutic method has demonstrated efficacy in managing CRC and mCRC, its broader clinical application is limited due to the unique physical properties, mechanisms of action, and pharmacokinetics of different chemotherapeutic drugs. Consequently, achieving satisfactory treatment outcomes proves to be challenging. Nanotechnology has given rise to innovative drug systems that are precise, controllable, and highly efficient in drug delivery. These nanoscale drug delivery systems can integrate the advantageous aspects of various therapeutic modalities, including chemotherapy, gene therapy, and immunotherapy. This review aims to explain the application of nano-drug delivery system in the treatment of colorectal cancer. Through its unique physical/chemical properties and biological functions, it can solve the limitations of traditional therapy and achieve more accurate, efficient and safe treatment. The advantages/disadvantages, physical and chemical characteristics of various drug delivery systems are described in detail, and suggestions on selecting reasonable NDDSs according to different drug combination methods are given to achieve the best therapeutic effect. This review paper presents an exhaustive summary of the diverse range of drugs utilized in chemotherapy, in addition to outlining strategies for effectively integrating chemotherapy with other treatment modalities. Furthermore, it delves into the principle of selecting carriers for various drug combinations.
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Affiliation(s)
- Liqi Li
- Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Maohua Chen
- Department of Pharmacy, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Rui L Reis
- 3Bs Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, Guimarães 4805-017, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães 4800-058, Portugal
| | - Subhas C Kundu
- 3Bs Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetic, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, Guimarães 4805-017, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães 4800-058, Portugal
| | - Bo Xiao
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China.
| | - Xiaoxiao Shi
- State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China.
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Long X, Wang J, Wang H, Hu K, Zhang W, Lin W, Fang C, Cheng K, Song Z. Injectable 2D-MoS 2-integrated Bioadhesive Hydrogel as Photothermal-Derived and Drug-Delivery Implant for Colorectal Cancer Therapy. Adv Healthc Mater 2025; 14:e2404842. [PMID: 40091342 PMCID: PMC12023830 DOI: 10.1002/adhm.202404842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/10/2025] [Indexed: 03/19/2025]
Abstract
Photothermal therapy (PTT) combined with chemotherapy using hydrogel as a delivery platform is considered a promising strategy for the treatment of advanced colorectal cancer (CRC). However, maintaining the stability of photo-absorbing agents (PTA) in the hydrogel and ensuring that the hydrogel remains anchored to the tumor tissue presents significant challenges. Herein, this work introduces an injectable 2D molybdenum disulfide (2D-MoS2)-integrated adhesive hydrogel, specifically N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitro-sophenoxy) butanamide-linked sodium alginate-MoS2-5-fluorouracil (AlgNB/MoS2/5-FU). This hydrogel functions as a near-infrared light (NIR)-triggered photothermal and drug-delivery implant for CRC treatment. The MoS2 nanosheets maintain superior dispersibility in the hydrogel and exhibit a highly efficient NIR-triggered photothermal effect. Importantly, the aldehyde group in AlgNB also imparted tissue adhesion to the hydrogel, the adhesive hydrogel is used to infiltrate and anchor within tumor tissue. The injectable adhesive AlgNB/MoS2/5-FU hydrogel shows remarkable efficacy in inhibiting SW480 cells proliferation and promoting colorectal tumor regression by triggering PTT and delivering the 5-FU drug in both in vitro and in vivo studies. The potential synergistic mechanism of PTT and 5-FU chemotherapy may contribute to inhibiting DNA repair and enhancing a robust immune response. Therefore, this research provides valuable strategic insights for the synergistic treatment of localized CRC.
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Affiliation(s)
- Xiaojun Long
- Department of Colorectal SurgeryKey Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China
| | - Jiawei Wang
- Department of Colorectal SurgeryKey Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China
| | - Huijuan Wang
- Department of Colorectal SurgeryKey Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China
| | - Kepeng Hu
- Department of Colorectal SurgeryKey Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China
| | - Wei Zhang
- Department of Colorectal SurgeryKey Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China
| | - Weiming Lin
- School of Materials Science and EngineeringState Key Laboratory of Silicon MaterialsCyrus Tang Center for Sensor Materials and ApplicationsZhejiang UniversityHangzhou310027China
| | - Chao Fang
- School of Materials Science and EngineeringState Key Laboratory of Silicon MaterialsCyrus Tang Center for Sensor Materials and ApplicationsZhejiang UniversityHangzhou310027China
| | - Kui Cheng
- School of Materials Science and EngineeringState Key Laboratory of Silicon MaterialsCyrus Tang Center for Sensor Materials and ApplicationsZhejiang UniversityHangzhou310027China
| | - Zhangfa Song
- Department of Colorectal SurgeryKey Laboratory of Biological Treatment of Zhejiang ProvinceSir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang310016China
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6
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Zhang B, Li M, Ji J, Si X, Yin X, Ji G, Ren L, Yao H. A syringeable immunotherapeutic hydrogel enhances T cell immunity via in-situ activation of STING pathway for advanced breast cancer postoperative therapy. Front Immunol 2025; 16:1523436. [PMID: 40176815 PMCID: PMC11961417 DOI: 10.3389/fimmu.2025.1523436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 02/26/2025] [Indexed: 04/04/2025] Open
Abstract
Complete surgical resection of advanced breast cancer is highly challenging and often leaves behind microscopic tumor foci, leading to inevitable relapse. Postoperative formation of the immunosuppressive tumor microenvironment (TME) reduces the efficacy of immunotherapies against residual tumors. Although cytotoxic chemotherapeutics exert the capacity to intensify cancer immunotherapy via immunogenic cell death (ICD) effects, systemically administered chemo agents often cannot access residual tumor sites, and fail to elicit antitumor immune responses. Herein, we present a novel syringeable immunotherapeutic hydrogel (SiGel@SN38/aOX40) loaded with the DNA-targeting chemotherapeutic 7-ethyl-10-hydroxycamptothecin (SN38) and the anti-OX40 agonist antibody (aOX40). The sustained in-site release of SN38 and aOX40 activate the stimulator of interferon genes (STING) pathway, intensify type I interferons expression, synergistically facilitate dendritic cell (DC) activation, and initiate persistent T cell mediated immune responses within the surgical resection bed that eliminate residual tumors with no tumor recurrence in 120 days. Collectively, our designed SiGel@SN38/aOX40 induces robust and long-lasting tumoricidal immunity following breast cancer resection and exhibit immense potential for clinical translation.
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Affiliation(s)
- Baozhen Zhang
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Min Li
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Jiahua Ji
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Xinghui Si
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
| | - Xiaojiao Yin
- Department of Gynecologic Oncology, Gynecology and Obstetrics Center, the First Hospital of Jilin University, Changchun, China
| | - Guofeng Ji
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Liqun Ren
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, China
| | - Haochen Yao
- Hepatobiliary and Pancreatic Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, China
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Tan Z, Tian L, Luo Y, Ai K, Zhang X, Yuan H, Zhou J, Ye G, Yang S, Zhong M, Li G, Wang Y. Preventing postsurgical colorectal cancer relapse: A hemostatic hydrogel loaded with METTL3 inhibitor for CAR-NK cell therapy. Bioact Mater 2025; 44:236-255. [PMID: 39497707 PMCID: PMC11532749 DOI: 10.1016/j.bioactmat.2024.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 10/16/2024] [Accepted: 10/16/2024] [Indexed: 11/07/2024] Open
Abstract
Colorectal cancer (CRC) recurrence post-surgery remains a major challenge. While Chimeric Antigen Receptor (CAR)-engineered natural killer (NK) cells hold immense therapeutic potential, their intratumoral infiltration ability remains limited, hampering efficacy. Building upon prior research suggesting that chemokines like C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) recruit CAR-NK cells, we hypothesized that tumor cell m6A methylation, regulated by Methyltransferase-like 3 (METTL3), influences chemokine secretion. This study aims to elucidate the underlying mechanisms and improve METTL3 inhibition efficiency. We designed an adhesive hemostasis hydrogel loaded with STM2457, a METTL3 inhibitor, aimed at sustained release in the acidic tumor microenvironment. In vitro, the hydrogel promoted CAR-NK cell recruitment and tumor killing via sustained METTL3 inhibition. The hydrogel's Schiff base bonds further enabled intestinal adhesion and hemostasis in an incomplete tumor resection model of CRC. Combining the hydrogel with CAR-NK cell therapy significantly reduced CRC recurrence in vivo. Overall, our study reveals the crucial role of METTL3 in CRC recurrence and proposes a promising, multimodal strategy using STM2457-loaded hydrogel and CAR-NK cells for enhanced therapeutic efficacy.
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Affiliation(s)
- Zilin Tan
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Liangjie Tian
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Yang Luo
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Road 160, Shanghai, 200127, China
| | - Kexin Ai
- Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xuehua Zhang
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Haitao Yuan
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Jinfan Zhou
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Guangyao Ye
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Road 160, Shanghai, 200127, China
| | - Shuofei Yang
- Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Road 160, Shanghai, 200127, China
| | - Ming Zhong
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Road 160, Shanghai, 200127, China
| | - Gaohua Li
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Yanan Wang
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
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Chen L, Yin Q, Zhang H, Zhang J, Yang G, Weng L, Liu T, Xu C, Xue P, Zhao J, Zhang H, Yao Y, Chen X, Sun S. Protecting Against Postsurgery Oral Cancer Recurrence with an Implantable Hydrogel Vaccine for In Situ Photoimmunotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2309053. [PMID: 39467056 PMCID: PMC11633475 DOI: 10.1002/advs.202309053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 08/20/2024] [Indexed: 10/30/2024]
Abstract
Oral squamous cell carcinoma (OSCC) often recurs aggressively and metastasizes despite surgery and adjuvant therapy, driven by postoperative residual cancer cells near the primary tumor site. An implantable in situ vaccine hydrogel was designed to target residual OSCC cells post-tumor removal. This hydrogel serves as a reservoir for the sustained localized release of δ-aminolevulinic acid (δ-ALA), enhancing protoporphyrin IX-mediated photodynamic therapy (PDT), and a polydopamine-hyaluronic acid composite for photothermal therapy (PTT). Additionally, immune adjuvants, including anti-CD47 antibodies (aCD47) and CaCO3 nanoparticles, are directly released into the resected tumor bed. This approach induces apoptosis of residual OSCC cells through sequential near-infrared irradiation, promoting calcium interference therapy (CIT). The hydrogel further stimulates immunogenic cell death (ICD), facilitating the polarization of tumor-associated macrophages from the M2 to the M1 phenotype. This facilitates phagocytosis, dendritic cell activation, robust antigen presentation, and cytotoxic T lymphocyte-mediated cytotoxicity. In murine OSCC models, the in situ vaccine effectively prevents local recurrence, inhibits orthotopic OSCC growth and pulmonary metastases, and provides long-term protective immunity against tumor rechalle nge. These findings support postoperative in situ vaccination with a biocompatible hydrogel implant as a promising strategy to minimize residual tumor burden and reduce recurrence risk after OSCC resection.
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Affiliation(s)
- Lan Chen
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Qiqi Yin
- School of Chemical Engineering and TechnologyShaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical EngineeringXi'an Jiaotong UniversityXi'an710049China
| | - Handan Zhang
- School of Chemical Engineering and TechnologyShaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical EngineeringXi'an Jiaotong UniversityXi'an710049China
| | - Jie Zhang
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Guizhu Yang
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Lin Weng
- School of Chemical Engineering and TechnologyShaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical EngineeringXi'an Jiaotong UniversityXi'an710049China
| | - Tao Liu
- School of Chemical Engineering and TechnologyShaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical EngineeringXi'an Jiaotong UniversityXi'an710049China
| | - Chenghui Xu
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Pengxin Xue
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Jinchao Zhao
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Han Zhang
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Yanli Yao
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
| | - Xin Chen
- School of Chemical Engineering and TechnologyShaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical EngineeringXi'an Jiaotong UniversityXi'an710049China
| | - Shuyang Sun
- Department of Oral and Maxillofacial‐Head Neck OncologyShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityShanghai200011China
- National Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyResearch Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai200011China
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9
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Sun L, Qi J, Ding L, Wang Z, Ji G, Zhang P. Ultrasound-triggered nano delivery of lenvatinib for selective immunotherapy treatment against hepatocellular carcinoma. Sci Rep 2024; 14:27395. [PMID: 39521911 PMCID: PMC11550808 DOI: 10.1038/s41598-024-79069-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024] Open
Abstract
Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy.
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Affiliation(s)
- Lu Sun
- Hepatobiliary and Pancreatic Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, China
| | - Jun Qi
- Hepatobiliary and Pancreatic Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, China
| | - Lei Ding
- Hepatobiliary and Pancreatic Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, China
| | - Zixuan Wang
- Hepatobiliary and Pancreatic Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, China
| | - Guofeng Ji
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
| | - Ping Zhang
- Hepatobiliary and Pancreatic Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, China.
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10
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Zheng W, Li J, Li J, Bie N, Wei Z, Qin J, Li S, Yong T, Du Q, Yang X, Gan L. In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis. J Control Release 2024; 375:316-330. [PMID: 39251139 DOI: 10.1016/j.jconrel.2024.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 08/09/2024] [Accepted: 09/05/2024] [Indexed: 09/11/2024]
Abstract
In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.
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Affiliation(s)
- Wenxia Zheng
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Jianye Li
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Jiaojiao Li
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Nana Bie
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Zhaohan Wei
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Jiaqi Qin
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Shiyu Li
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Tuying Yong
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Qing Du
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China.
| | - Xiangliang Yang
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China.
| | - Lu Gan
- National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China.
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11
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Sun M, Shi T, Tuerhong S, Li M, Wang Q, Lu C, Zou L, Zheng Q, Wang Y, Du J, Li R, Liu B, Meng F. An Immunomodulator-Boosted Lactococcus Lactis Platform For Enhanced In Situ Tumor Vaccine. Adv Healthc Mater 2024; 13:e2401635. [PMID: 39054611 DOI: 10.1002/adhm.202401635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 07/15/2024] [Indexed: 07/27/2024]
Abstract
In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.
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Affiliation(s)
- Mengna Sun
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Tianyu Shi
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Subiyinuer Tuerhong
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Mengru Li
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Qiaoli Wang
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Changchang Lu
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Lu Zou
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Qinghua Zheng
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital,Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science, Nanjing Normal University, Nanjing, 210008, China
| | - Yingxin Wang
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Juan Du
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Rutian Li
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Baorui Liu
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Fanyan Meng
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
- Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
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12
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Wang J, Sun X, Zhao Z, Wang G, Wang D, Li Y. Confined copper depletion via a hydrogel platform for reversing dabrafenib/cetuximab resistance in BRAF V600E-mutant colorectal cancer. J Control Release 2024; 375:643-653. [PMID: 39306044 DOI: 10.1016/j.jconrel.2024.09.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 09/14/2024] [Accepted: 09/18/2024] [Indexed: 09/26/2024]
Abstract
BRAFV600E-mutant colorectal cancer (CRC) is resistant to most first-line therapeutics, including the BRAF inhibitor dabrafenib and epidermal growth factor receptor (EGFR) inhibitor cetuximab. Although copper depletion shows promise in reversing dabrafenib/cetuximab resistance in BRAFV600E-mutant CRC, its application is limited by the potential for excessive copper depletion in non-tumor objects. In this study, we have developed a hydrogel platform for confined copper depletion in BRAFV600E-mutant CRC cells, which effectively reverses dabrafenib/cetuximab resistance and enhancing therapeutic efficiency. The hydrogel platform enables precise intracellular copper depletion through localized administration, acidity-triggered drug release, and oxidized activation of a copper prochelator. The dosage of this prochelator is 37.5 μg/kg in mouse models, which is significantly lower than the commonly used tetrathiomolybdate. Furthermore, both dabrafenib and the prochelator are preloaded into acid-responsive nanoparticles before being embedded in the hydrogel matrix to facilitate efficient endocytosis and acid-activatable drug release. Confined copper depletion inhibits MEK1 signaling and suppresses the MAPK signaling pathway when combined with BRAF and EGFR inhibitors. Moreover, the hydrogel platform inhibits tumor growth and prolongs survival in subcutaneous and postsurgical models of BRAFV600E-mutant CRC. This study provides an innovative strategy for overcoming dabrafenib/cetuximab resistance in BRAFV600E-mutant CRC through precise intracellular copper depletion.
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Affiliation(s)
- Jue Wang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiangshi Sun
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Zhiwen Zhao
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guanru Wang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Dangge Wang
- Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
| | - Yaping Li
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Shandong 264117, China.
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13
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Sun S, Wang Q, Zhang B, Cui Y, Si X, Wang G, Wang J, Xu H, Yuan B, Peng C. Vancomycin-Loaded in situ Gelled Hydrogel as an Antibacterial System for Enhancing Repair of Infected Bone Defects. Int J Nanomedicine 2024; 19:10227-10245. [PMID: 39411352 PMCID: PMC11476785 DOI: 10.2147/ijn.s448876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 03/19/2024] [Indexed: 10/19/2024] Open
Abstract
Purpose During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix. Methods In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments. Results The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher (p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher (p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group (p < 0.01). Conclusion In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.
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Affiliation(s)
- Shouye Sun
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Qian Wang
- Department of Otolaryngology, The First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Bin Zhang
- Department of Spinal Surgery, The 964th Hospital of PLA Joint Logistic Support Force, Changchun, People’s Republic of China
| | - Yutao Cui
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Xinghui Si
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of China
| | - Gan Wang
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Jingwei Wang
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Hang Xu
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Baoming Yuan
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Chuangang Peng
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
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14
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Zhou A, Jia J, Ji X, Cheng S, Song X, Hu J, Zhao Y, Yu L, Wang J, Wang F. Reshaped Local and Systemic Immune Responses Triggered by a Biomimetic Multifunctional Nanoplatform Coordinating Multi-Pathways for Cancer Therapy. ACS APPLIED MATERIALS & INTERFACES 2024. [PMID: 39356986 DOI: 10.1021/acsami.4c05714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/04/2024]
Abstract
Immunotherapy has fundamentally transformed the clinical cancer treatment landscape; however, achieving intricate and multifaceted modulation of the immune systems remains challenging. Here, a multipathway coordination of immunogenic cell death (ICD), autophagy, and indoleamine 2,3-dioxygenase-1 (IDO1) was achieved by a biomimetic nano-immunomodulator assembled from a chemotherapeutic agent (doxorubicin, DOX), small interfering RNA (siRNA) molecules targeting IDO1 (siIDO1), and the zeolitic imidazolate framework-8 (ZIF-8). After being camouflaged with a macrophage membrane, the biomimetic nanosystem, named mRDZ, enriched in tumors, which allowed synergistic actions of its components within tumor cells. The chemotherapeutic intervention led to a compensatory upregulation in the expression of IDO1, consequently exerting an inhibitory effect on the reactive oxygen species (ROS) and autophagic responses triggered by DOX and ZIF-8. Precise gene silencing of IDO1 by siIDO1 alleviated its suppressive influence, thereby facilitating increased ROS production and improved autophagy, ultimately bolstering tumor immunogenicity. mRDZ exhibited strong capability to boost potent local and systemic antitumor immune responses with a feature of memory, which led to the effective suppression of the growth, lung metastasis, and recurrence of the tumor. Serving as an exemplary model for the straightforward and potent reshaping of the immune system against tumors, mRDZ offers valuable insights into the development of immunomodulatory nanomaterials for cancer therapy.
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Affiliation(s)
- Ao Zhou
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Jingyan Jia
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Xueyang Ji
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Sunying Cheng
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Xiaoxin Song
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Jingyan Hu
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Yan Zhao
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
| | - Luying Yu
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Jieting Wang
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Fang Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
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15
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Si X, Ji G, Ma S, Huang Z, Liu T, Shi Z, Zhang Y, Li J, Song W, Chen X. Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2405935. [PMID: 39116306 PMCID: PMC11481255 DOI: 10.1002/advs.202405935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/06/2024] [Indexed: 08/10/2024]
Abstract
Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor-specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4-arm polyethylene glycol hydroxylamine (4-arm PEG-ONH2) through oxime bonds, which can be injected through a clinic-used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.
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Affiliation(s)
- Xinghui Si
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- Jilin Biomedical Polymers Engineering LaboratoryChangchun130022China
| | - Guofeng Ji
- Department of General Surgery, Xuanwu HospitalCapital Medical UniversityBeijing100053China
| | - Sheng Ma
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- Jilin Biomedical Polymers Engineering LaboratoryChangchun130022China
| | - Zichao Huang
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- School of Applied Chemistry and EngineeringUniversity of Science and Technology of ChinaHefei230026China
| | - Taiyuan Liu
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- The Second Hospital of Jilin UniversityChangchun130000China
| | - Zhiyuan Shi
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- School of Applied Chemistry and EngineeringUniversity of Science and Technology of ChinaHefei230026China
| | - Yu Zhang
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- Jilin Biomedical Polymers Engineering LaboratoryChangchun130022China
| | - Jia Li
- Department of General Surgery, Xuanwu HospitalCapital Medical UniversityBeijing100053China
| | - Wantong Song
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- Jilin Biomedical Polymers Engineering LaboratoryChangchun130022China
- School of Applied Chemistry and EngineeringUniversity of Science and Technology of ChinaHefei230026China
| | - Xuesi Chen
- Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China
- Jilin Biomedical Polymers Engineering LaboratoryChangchun130022China
- School of Applied Chemistry and EngineeringUniversity of Science and Technology of ChinaHefei230026China
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Goswami R, Nabawy A, Jiang M, Cicek YA, Hassan MA, Nagaraj H, Zhang X, Rotello VM. All-Natural Gelatin-Based Nanoemulsion Loaded with TLR 7/8 Agonist for Efficient Modulation of Macrophage Polarization for Immunotherapy. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:1556. [PMID: 39404283 PMCID: PMC11477480 DOI: 10.3390/nano14191556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/23/2024] [Accepted: 09/25/2024] [Indexed: 10/19/2024]
Abstract
Macrophages are multifunctional immune cells essential for both innate and adaptive immune responses. Tumor-associated macrophages (TAMs) often adopt a tumor-promoting M2-like phenotype, aiding tumor progression and immune evasion. Reprogramming TAMs to a tumoricidal M1-like phenotype is an emerging target for cancer immunotherapy. Resiquimod, a TLR7/8 agonist, can repolarize macrophages from the M2- to M1-like phenotype but is limited by poor solubility. We developed a gelatin nanoemulsion for the loading and delivery of resiquimod, utilizing eugenol oil as the liquid phase and riboflavin-crosslinked gelatin as a scaffold. These nanoemulsions showed high stability, low toxicity, and effective macrophage repolarization, significantly enhancing pro-inflammatory markers and anticancer activity in co-culture models.
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Affiliation(s)
| | | | | | | | | | | | | | - Vincent M Rotello
- Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA (M.J.); (Y.A.C.); (H.N.)
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17
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Shi Z, Gao Z, Zhuang X, Si X, Huang Z, Di Y, Ma S, Guo Z, Li C, Jin N, Huang L, Tian M, Song W, Chen X. Dynamic Covalent Hydrogel as a Single-Dose Vaccine Adjuvant for Sustained Antigen Release and Significantly Elevated Humoral Immunity. Adv Healthc Mater 2024; 13:e2400886. [PMID: 38824421 DOI: 10.1002/adhm.202400886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/30/2024] [Indexed: 06/03/2024]
Abstract
Vaccine is the most important way for fighting against infection diseases. However, multiple injections and unsatisfied immune responses are the main obstacles for current vaccine application. Herein, a dynamic covalent hydrogel (DCH) is used as a single-dose vaccine adjuvant for eliciting robust and sustained humoral immunity. By adjusting the mass ratio of the DCH gel, 10-30 d constant release of the loaded recombinant protein antigens is successfully realized, and it is proved that sustained release of antigens can significantly improve the vaccine efficacy. When loading SARS-CoV-2 RBD (Wuhan and Omicron BA.1 strains) antigens into this DCH gel, an over 32 000 times and 8000 times improvement is observed in antigen-specific antibody titers compared to conventional Aluminum adjuvanted vaccines. The universality of this DCH gel adjuvant is confirmed in a Nipah G antigen test as well as a H1N1 influenza virus antigen test, with much improved protection of C57BL/6 mice against H1N1 virus infection than conventional Aluminum adjuvanted vaccines. This sustainably released, single-dose DCH gel adjuvant provides a new promising option for designing next-generation infection vaccines.
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MESH Headings
- Animals
- Hydrogels/chemistry
- Mice, Inbred C57BL
- Mice
- Immunity, Humoral/drug effects
- Influenza A Virus, H1N1 Subtype/immunology
- SARS-CoV-2/immunology
- Antigens, Viral/immunology
- Adjuvants, Immunologic/pharmacology
- Adjuvants, Immunologic/chemistry
- Adjuvants, Immunologic/administration & dosage
- Adjuvants, Vaccine/chemistry
- Antibodies, Viral/immunology
- Antibodies, Viral/blood
- COVID-19/prevention & control
- COVID-19/immunology
- COVID-19 Vaccines/immunology
- COVID-19 Vaccines/chemistry
- COVID-19 Vaccines/administration & dosage
- Female
- Humans
- Influenza Vaccines/immunology
- Influenza Vaccines/chemistry
- Influenza Vaccines/administration & dosage
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Affiliation(s)
- Zhiyuan Shi
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
| | - Zihan Gao
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Xinyu Zhuang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Xinghui Si
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
| | - Zichao Huang
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
| | - Yaxin Di
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Sheng Ma
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
| | - Zhaopei Guo
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
| | - Chang Li
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Ningyi Jin
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Leaf Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina, 27599, USA
| | - Mingyao Tian
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Wantong Song
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
| | - Xuesi Chen
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, China
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18
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Zhuo Y, Zeng H, Su C, Lv Q, Cheng T, Lei L. Tailoring biomaterials for vaccine delivery. J Nanobiotechnology 2024; 22:480. [PMID: 39135073 PMCID: PMC11321069 DOI: 10.1186/s12951-024-02758-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 08/06/2024] [Indexed: 08/15/2024] Open
Abstract
Biomaterials are substances that can be injected, implanted, or applied to the surface of tissues in biomedical applications and have the ability to interact with biological systems to initiate therapeutic responses. Biomaterial-based vaccine delivery systems possess robust packaging capabilities, enabling sustained and localized drug release at the target site. Throughout the vaccine delivery process, they can contribute to protecting, stabilizing, and guiding the immunogen while also serving as adjuvants to enhance vaccine efficacy. In this article, we provide a comprehensive review of the contributions of biomaterials to the advancement of vaccine development. We begin by categorizing biomaterial types and properties, detailing their reprocessing strategies, and exploring several common delivery systems, such as polymeric nanoparticles, lipid nanoparticles, hydrogels, and microneedles. Additionally, we investigated how the physicochemical properties and delivery routes of biomaterials influence immune responses. Notably, we delve into the design considerations of biomaterials as vaccine adjuvants, showcasing their application in vaccine development for cancer, acquired immunodeficiency syndrome, influenza, corona virus disease 2019 (COVID-19), tuberculosis, malaria, and hepatitis B. Throughout this review, we highlight successful instances where biomaterials have enhanced vaccine efficacy and discuss the limitations and future directions of biomaterials in vaccine delivery and immunotherapy. This review aims to offer researchers a comprehensive understanding of the application of biomaterials in vaccine development and stimulate further progress in related fields.
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Affiliation(s)
- Yanling Zhuo
- College of Intelligent Agriculture, Yulin Normal University, Yulin, 537000, China
| | - Huanxuan Zeng
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325200, China
| | - Chunyu Su
- College of Intelligent Agriculture, Yulin Normal University, Yulin, 537000, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, China
| | - Qizhuang Lv
- College of Intelligent Agriculture, Yulin Normal University, Yulin, 537000, China.
- College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, China.
- Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin, 537000, China.
| | - Tianyin Cheng
- College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, China.
| | - Lanjie Lei
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, China.
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Wu C, Zhang H, Guo Y, Sun X, Hu Z, Teng L, Zeng Z. Porous Hydrogels for Immunomodulatory Applications. Int J Mol Sci 2024; 25:5152. [PMID: 38791191 PMCID: PMC11121438 DOI: 10.3390/ijms25105152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/02/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024] Open
Abstract
Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.
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Affiliation(s)
- Cuifang Wu
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
| | - Honghong Zhang
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
| | - Yangyang Guo
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
| | - Xiaomin Sun
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
| | - Zuquan Hu
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
| | - Lijing Teng
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
| | - Zhu Zeng
- Key Laboratory of Infectious Immune and Antibody Engineering in University of Guizhou Province, Engineering Research Center of Cellular Immunotherapy of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China; (C.W.)
- Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550025, China
- Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang 550004, China
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20
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Li H, Wang Z, Chu X, Zhao Y, He G, Hu Y, Liu Y, Wang ZL, Jiang P. Free Radicals Generated in Perfluorocarbon-Water (Liquid-Liquid) Interfacial Contact Electrification and Their Application in Cancer Therapy. J Am Chem Soc 2024; 146:12087-12099. [PMID: 38647488 DOI: 10.1021/jacs.4c02149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
Electron transfer during solid-liquid contact electrification has been demonstrated to produce reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and superoxide anion radicals (•O2-). Here, we show that such a process also occurs in liquid-liquid contact electrification. By preparing perfluorocarbon nanoemulsions to construct a perfluorocarbon-water "liquid-liquid" interface, we confirmed that electrons were transferred from water to perfluorocarbon in ultrasonication-induced high-frequency liquid-liquid contact to produce •OH and •O2-. The produced ROS could be applied to ablate tumors by triggering large-scale immunogenic cell death in tumor cells, promoting dendritic cell maturation and macrophage polarization, ultimately activating T cell-mediated antitumor immune response. Importantly, the raw material for producing •OH is water, so the tumor therapy is not limited by the endogenous substances (O2, H2O2, etc.) in the tumor microenvironment. This work provides new perspectives for elucidating the mechanism of generation of free radicals in liquid-liquid contact and provides an excellent tumor therapeutic modality.
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Affiliation(s)
- Haimei Li
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), Wuhan University, Wuhan 430072, China
| | - Zichen Wang
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Xu Chu
- State Key Laboratory of Separation Membrane and Membrane Process & Tianjin Key Laboratory of Green Chemical Technology and Process Engineering, School of Chemistry and Chemical Engineering, Tiangong University, Tianjin 300387, China
| | - Yi Zhao
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Guangqin He
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Yulin Hu
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Yi Liu
- State Key Laboratory of Separation Membrane and Membrane Process & Tianjin Key Laboratory of Green Chemical Technology and Process Engineering, School of Chemistry and Chemical Engineering, Tiangong University, Tianjin 300387, China
- School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Zhong Lin Wang
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 100083, China
| | - Peng Jiang
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), Wuhan University, Wuhan 430072, China
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21
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Wang Z, Dong M, Pan Y, Zhang L, Lei H, Zheng Y, Shi Y, Liu S, Li N, Wang Y. Turning Threat to Therapy: A Nanozyme-Patch in Surgical Bed for Convenient Tumor Vaccination by Sustained In Situ Catalysis. Adv Healthc Mater 2024; 13:e2304384. [PMID: 38301259 DOI: 10.1002/adhm.202304384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 01/27/2024] [Indexed: 02/03/2024]
Abstract
Complete surgical resection of tumor is difficult as the invasiveness of cancer, making the residual tumor a lethal threat to patients. The situation is deteriorated by the immune suppression state after surgery, which further nourishes tumor recurrence and metastasis. Immunotherapy is promising to combat tumor metastasis, but is limited by severe toxicity of traditional immunostimulants and complexity of multiple functional units. Here, it is reported that the simple "trans-surgical bed" delivery of Cu2- xSe nanozyme (CSN) by a microneedle-patch can turn the threat to therapy by efficient in situ vaccination. The biocompatible CSN exhibits both peroxidase and glutathione oxidase-like activities, efficiently exhausting glutathione, boosting free radical generation, and inducing immunogenic cell death. The once-for-all inserting of the patch on surgical bed facilitates sustained catalytic action, leading to drastic decrease of recurrence rate and complete suppression of tumor-rechallenge in cured mice. In vivo mechanism interrogation reveals elevated cytotoxic T cell infiltration, re-educated macrophages, increased dendritic cell maturation, and memory T cells formation. Importantly, preliminary metabolism and safety evaluation validated that the metal accumulation is marginable, and the important biochemical indexes are in normal range during therapy. This study has provided a simple, safe, and robust tumor vaccination approach for postsurgical metastasis control.
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Affiliation(s)
- Zhaohui Wang
- State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
| | - Min Dong
- State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
| | - Yuhang Pan
- State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
| | - Lu Zhang
- State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
| | - Haozhuo Lei
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Yuanzhe Zheng
- State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
| | - Yanbin Shi
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Shuang Liu
- Analytical Instrumentation Center, Institute of Deep-Sea Science and Engineering, Chinese Academy of Sciences, Sanya, 572000, China
- Deep-Sea Sci-Tech Core Facilities Sharing Platform, Sanya Yazhou Bay Science and Technology City, Sanya, 572000, China
| | - Nan Li
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China
| | - Yalong Wang
- State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
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Li B, Zhang P, Li J, Zhou R, Zhou M, Liu C, Liu X, Chen L, Li L. Allogeneic "Zombie Cell" as Off-The-Shelf Vaccine for Postsurgical Cancer Immunotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2307030. [PMID: 38279587 PMCID: PMC10987105 DOI: 10.1002/advs.202307030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 12/18/2023] [Indexed: 01/28/2024]
Abstract
Allogeneic tumor cell vaccines provide off-the-shelf convenience but lack patient specificity due to heterogeneity in tumor antigens. Here, allogeneic tumor cell corpses are converted into "zombie cells" capable of assimilating heterogeneous tumor by seizing cancer cells and spreading adjuvant infection. This causes pseudo-oncolysis of tumors, transforming them into immunogenic targets for enhanced phagocytosis. It is shown that in postoperative tumor models, localized delivery of premade "zombie cells" through stepwise gelation in resection cavity consolidates tumor surgery. Compared to analogous vaccines lacking "seizing" or "assimilating" capability, "zombie cell" platform effectively mobilizes T cell response against residual tumors, and establishes immunological memory against tumor re-challenge, showing less susceptibility to immune evasion. Despite using allogeneic sources, "zombie cell" platform functions as generalizable framework to produce long-term antitumor immunity in different tumor models, showing comparable effect to autologous vaccine. Together, with the potential of off-the-shelf availability and personalized relevance to heterogenous tumor antigens, this study suggests an alternative strategy for timely therapy after tumor surgery.
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Affiliation(s)
- Bo Li
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Ping Zhang
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Junlin Li
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Rui Zhou
- NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo CorrelationSichuan Institute for Drug ControlChengdu611730China
| | - Minglu Zhou
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Chendong Liu
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Xi Liu
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Liqiang Chen
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
| | - Lian Li
- Key Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant‐Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China
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Liu H, Shi Y, Ji G, Wang J, Gai B. Ultrasound-triggered with ROS-responsive SN38 nanoparticle for enhanced combination cancer immunotherapy. Front Immunol 2024; 15:1339380. [PMID: 38571953 PMCID: PMC10987707 DOI: 10.3389/fimmu.2024.1339380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 02/29/2024] [Indexed: 04/05/2024] Open
Abstract
Controlled generation of cytotoxic reactive oxygen species (ROS) is essential in cancer therapy. Ultrasound (US)-triggered sonodynamic therapy (SDT) has shown considerable ability to trigger in situ ROS generation. Unfortunately, US therapy alone is insufficient to trigger an efficient anticancer response, owing to the induction of multiple immunosuppressive factors. It was identified that 7-ethyl-10-hydroxycamptothecin (SN38) could notably inhibit DNA topoisomerase I, induce DNA damage and boost robust anticancer immunity. However, limited by the low metabolic stability, poor bioavailability, and dose-limiting toxicity, the direct usage of SN38 is inadequate in immune motivation, which limits its clinical application. Hence, new strategies are needed to improve drug delivery efficiency to enhance DNA topoisomerase I inhibition and DNA damage and elicit a vigorous anticancer cancer immunity response. Considering US irradiation can efficiently generate large amounts of ROS under low-intensity irradiation, in this study, we aimed to design a polymeric, ROS-responsive SN38 nanoformulation for in vivo drug delivery. Upon the in-situ generation of ROS by US therapy, controlled on-demand release of SN38 occurred in tumor sites, which enhanced DNA damage, induced DC cell maturation, and boosted anticancer immunity. Our results demonstrated that a new strategy of involving the combination of a SN38 nanoformulation and US therapy could be used for cancer immunotherapy.
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Affiliation(s)
- Hongyu Liu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yunpeng Shi
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Guofeng Ji
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jukun Wang
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Baodong Gai
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union of Jilin University, Changchun, China
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24
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Wu Z, Zhou S, Liang D, Mu L. GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/β-catenin pathway in colorectal cancer cells. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:1115-1125. [PMID: 37610461 DOI: 10.1007/s00210-023-02668-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/09/2023] [Indexed: 08/24/2023]
Abstract
Colorectal carcinoma (CRC) is a common cancer associated with poor prognosis, and cudraflavone C (Cud C) is a natural flavonol with reported anti-CRC capacity. However, the precise mechanisms underlying the anti-CRC effect require further demonstration. The aim of present study was to evaluate the impact of Cud C on the cell viability and apoptosis of CRC cells and to determine the underlying mechanisms. The Human Protein Atlas (THPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze the expression status of glutathione peroxidase 2 (GPX2) in CRC. Cell viability was examined using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to evaluate apoptosis. The levels of gene transcription and protein expression of GPX2, caspase-3, cleaved caspase-3), β-catenin, and c-Myc were determined by RT-qPCR and Western blotting. Our results showed that GPX2 was overexpressed in CRC as compared to normal tissue and the extent of GPX2 overexpression is greatest in CRC when compared with other cancers according to GEPIA and THPA databases. GPX2 knockdown significantly suppressed the cell viability, induced apoptosis of CRC cell lines, and restrained the activity of Wnt/β-catenin pathway. Cud C treatment decreased cell viability, induced apoptosis in CRC cell lines, and diminished the expression level of GPX2-dependent activation of Wnt/β-catenin pathway, while such effects can be abolished by GPX2 overexpression. In conclusion, Cud C suppressed GPX2-dependent Wnt/β-catenin pathway to exert anti-CRC function.
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Affiliation(s)
- Zhuo Wu
- Uutpatient Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China
| | - Su Zhou
- Department of Drug Management, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China
| | - Dan Liang
- Department of Otolaryngology, the First Affiliated Hospital of Jinzhou Medical University, 5-2 Renmin Street, Jinzhou, People's Republic of China
| | - Lan Mu
- Department of Otolaryngology, the First Affiliated Hospital of Jinzhou Medical University, 5-2 Renmin Street, Jinzhou, People's Republic of China.
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25
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Liu T, Si X, Liu L, Ma S, Huang Z, Zhang Y, Song W, Zhang Y, Chen X. Injectable Nano-in-Gel Vaccine for Spatial and Temporal Control of Vaccine Kinetics and Breast Cancer Postsurgical Therapy. ACS NANO 2024; 18:3087-3100. [PMID: 38235966 DOI: 10.1021/acsnano.3c08376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2024]
Abstract
Breast cancer is the most commonly diagnosed cancer, and surgical resection is the first choice for its treatment. With the development of operation techniques, surgical treatment for breast cancer is evolving toward minimally invasive and breast-conserving approaches. However, breast-conserving surgery is prone to an increased risk of cancer recurrence and is becoming a key challenge that needs to be solved. In this study, we introduce a one-shot injectable nano-in-gel vaccine (NIGel-Vax) for postoperative breast cancer therapy. The NIGel-Vax was constructed by mixing protein antigens with PEI-4BImi-Man adjuvant and then encapsulated in a hydrogel made with oxidized dextran (ODEX) and 4-arm PEG-ONH2. Using 4T1 tumor-extracted proteins as antigen, the NIGel-Vax achieved a 92% tumor suppression rate and a 33% cure rate as a postoperative therapy in the 4T1 tumor model. Using the tumor-associated antigen trophoblast cell-surface antigen 2 (TROP2) protein as the antigen, NIGel-Vax achieved a 96% tumor suppression rate and a 50% cure rate in triple-negative breast cancer (TNBC) models. This design provides an encouraging approach for breast cancer postoperative management.
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Affiliation(s)
- Taiyuan Liu
- Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China
| | - Xinghui Si
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Liping Liu
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Sheng Ma
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Zichao Huang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Yu Zhang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Wantong Song
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Yingchao Zhang
- Department of Breast Surgery, Second Hospital of Jilin University, Changchun 130041, China
| | - Xuesi Chen
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
- Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
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Chen Z, Yong T, Wei Z, Zhang X, Li X, Qin J, Li J, Hu J, Yang X, Gan L. Engineered Probiotic-Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2305081. [PMID: 38009498 PMCID: PMC10797439 DOI: 10.1002/advs.202305081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/23/2023] [Indexed: 11/29/2023]
Abstract
Cancer vaccines hold great potential for clinical cancer treatment by eliciting T cell-mediated immunity. However, the limited numbers of antigen-presenting cells (APCs) at the injection sites, the insufficient tumor antigen phagocytosis by APCs, and the presence of a strong tumor immunosuppressive microenvironment severely compromise the efficacy of cancer vaccines. Trained innate immunity may promote tumor antigen-specific adaptive immunity. Here, a personalized cancer vaccine is developed by engineering the inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens and β-glucan, a trained immunity inducer. After subcutaneous injection, the cancer vaccine delivering model antigen OVA (BG/OVA@EcN) is highly accumulated and phagocytosed by macrophages at the injection sites to induce trained immunity. The trained macrophages may recruit dendritic cells (DCs) to facilitate BG/OVA@EcN phagocytosis and the subsequent DC maturation and T cell activation. In addition, BG/OVA@EcN remarkably enhances the circulating trained monocytes/macrophages, promoting differentiation into M1-like macrophages in tumor tissues. BG/OVA@EcN generates strong prophylactic and therapeutic efficacy to inhibit tumor growth by inducing potent adaptive antitumor immunity and long-term immune memory. Importantly, the cancer vaccine delivering autologous tumor antigens efficiently prevents postoperative tumor recurrence. This platform offers a facile translatable strategy to efficiently integrate trained immunity and adaptive immunity for personalized cancer immunotherapy.
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Affiliation(s)
- Zhaoxia Chen
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
| | - Tuying Yong
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Key Laboratory of Molecular Biophysics of the Ministry of EducationCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia MedicaHuazhong University of Science and TechnologyWuhan430074China
| | - Zhaohan Wei
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
| | - Xiaoqiong Zhang
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
| | - Xin Li
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
| | - Jiaqi Qin
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
| | - Jianye Li
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
| | - Jun Hu
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Key Laboratory of Molecular Biophysics of the Ministry of EducationCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia MedicaHuazhong University of Science and TechnologyWuhan430074China
| | - Xiangliang Yang
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Key Laboratory of Molecular Biophysics of the Ministry of EducationCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia MedicaHuazhong University of Science and TechnologyWuhan430074China
| | - Lu Gan
- National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Key Laboratory of Molecular Biophysics of the Ministry of EducationCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia MedicaHuazhong University of Science and TechnologyWuhan430074China
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Zhang Z, He C, Chen X. Designing Hydrogels for Immunomodulation in Cancer Therapy and Regenerative Medicine. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2308894. [PMID: 37909463 DOI: 10.1002/adma.202308894] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/26/2023] [Indexed: 11/03/2023]
Abstract
The immune system not only acts as a defense against pathogen and cancer cells, but also plays an important role in homeostasis and tissue regeneration. Targeting immune systems is a promising strategy for efficient cancer treatment and regenerative medicine. Current systemic immunomodulation therapies are usually associated with low persistence time, poor targeting to action sites, and severe side effects. Due to their extracellular matrix-mimetic nature, tunable properties and diverse bioactivities, hydrogels are intriguing platforms to locally deliver immunomodulatory agents and cells, as well as provide an immunomodulatory microenvironment to recruit, activate, and expand host immune cells. In this review, the design considerations, including polymer backbones, crosslinking mechanisms, physicochemical nature, and immunomodulation-related components, of the hydrogel platforms, are focused on. The immunomodulatory effects and therapeutic outcomes in cancer therapy and tissue regeneration of different hydrogel systems are emphasized, including hydrogel depots for delivery of immunomodulatory agents, hydrogel scaffolds for cell delivery, and immunomodulatory hydrogels depending on the intrinsic properties of materials. Finally, the remained challenges in current systems and future development of immunomodulatory hydrogels are discussed.
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Affiliation(s)
- Zhen Zhang
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
| | - Chaoliang He
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Xuesi Chen
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China
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Ling H, Zhang Q, Luo Q, Ouyang D, He Z, Sun J, Sun M. Dynamic immuno-nanomedicines in oncology. J Control Release 2024; 365:668-687. [PMID: 38042376 DOI: 10.1016/j.jconrel.2023.11.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/11/2023] [Accepted: 11/27/2023] [Indexed: 12/04/2023]
Abstract
Anti-cancer therapeutics have achieved significant advances due to the emergence of immunotherapies that rely on the identification of tumors by the patients' immune system and subsequent tumor eradication. However, tumor cells often escape immunity, leading to poor responsiveness and easy tolerance to immunotherapy. Thus, the potentiated anti-tumor immunity in patients resistant to immunotherapies remains a challenge. Reactive oxygen species-based dynamic nanotherapeutics are not new in the anti-tumor field, but their potential as immunomodulators has only been demonstrated in recent years. Dynamic nanotherapeutics can distinctly enhance anti-tumor immune response, which derives the concept of the dynamic immuno-nanomedicines (DINMs). This review describes the pivotal role of DINMs in cancer immunotherapy and provides an overview of the clinical realities of DINMs. The preclinical development of emerging DINMs is also outlined. Moreover, strategies to synergize the antitumor immunity by DINMs in combination with other immunologic agents are summarized. Last but not least, the challenges and opportunities related to DINMs-mediated immune responses are also discussed.
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Affiliation(s)
- Hao Ling
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
| | - Qinyi Zhang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
| | - Qiuhua Luo
- Department of Pharmacy, The First Hospital of China Medical University, Shenyang 110001, China
| | - Defang Ouyang
- Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
| | - Zhonggui He
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
| | - Jin Sun
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
| | - Mengchi Sun
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
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Li Y, Zhu J, Yang Y, Chen Y, Liu L, Tao J, Chen H, Deng Y. Long-Acting Nanohybrid Hydrogel Induces Persistent Immunogenic Chemotherapy for Suppressing Postoperative Tumor Recurrence and Metastasis. Mol Pharm 2023; 20:6345-6357. [PMID: 37942616 DOI: 10.1021/acs.molpharmaceut.3c00746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
Despite the continuous advancement of surgical resection techniques, postoperative tumor recurrence and metastasis remain a huge challenge. Here, we constructed an injectable curcumin/doxorubicin-loaded nanoparticle (NanoCD) hydrogel, which could effectively inhibit tumor regrowth and metastasis via reshaping the tumor immune microenvironment (TIME) for highly effective postsurgical cancer treatment. NanoCD was prepared by the controlled assembly of curcumin (CUR) and doxorubicin (DOX) via π-π stacking and hydrogen bonding in the presence of human serum albumin. To facilitate prolonged treatment of postsurgical tumors, NanoCD was further incorporated into the temperature-sensitive Poloxamer 407 gel (NanoCD@Gel) for intracavity administration. Mechanistically, DOX induced the generation of intracellular reactive oxygen species (ROS) and CUR reduced the ROS metabolism by inhibiting thioredoxin reductase (TrxR). The synergy of DOX and CUR amplified intracellular ROS levels and thus resulted in enhanced immunogenic cell death (ICD) of tumor cells. Upon being injected into the tumor cavity after resection, the in situ-generated NanoCD@Gel allowed the local release of CUR and DOX in a controlled manner to induce local chemotherapy and persistently activate the antitumor immune response, thereby achieving enhanced immunogenic chemotherapy with reduced systemic toxicity. Our work provides an elegant strategy for persistently stimulating effective antitumor immunity to prevent postsurgical tumor recurrence and metastasis.
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Affiliation(s)
- Yaoqi Li
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Jie Zhu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Yifan Yang
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Yitian Chen
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Lishan Liu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Jing Tao
- Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Huabing Chen
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
- State Key Laboratory of Radiation Medicine and Protection, and School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China
- Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yibin Deng
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
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Ma G, Li F, Wang X, Li Q, Hong Y, Wei Q, Gao F, Zhang W, Guo Y, Ma X, Hu Z. A Bionic Yeast Tumor Vaccine Using the Co-Loading Strategy to Prevent Post-Operative Tumor Recurrence. ACS NANO 2023; 17:21394-21410. [PMID: 37870500 DOI: 10.1021/acsnano.3c06115] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
Immunotherapy is an effective adjunct to surgery for preventing tumor recurrence and metastasis in postoperative tumor patients. Although mimicking microbial invasion and immune activation pathways can effectively stimulate the immune system, the limited capacity of microbial components to bind antigens and adjuvants restricts the development of this system. Here, we construct bionic yeast carriers (BYCs) by in situ polymerization of mesoporous silica nanoparticles (MSNs) within the yeast capsules (YCs). BYCs can mimic the yeast infection pathway while utilizing the loading capacity of MSNs for multiple substances. Pore size and hydrophobicity-modified BYC can be loaded with both antigen and adjuvant R848. Oral or subcutaneous injection uptake of coloaded BYCs demonstrated positive therapeutic effects as a tumor therapeutic vaccine in both the transplantation tumor model and the metastasis tumor model. 57% of initial 400 mm3 tumor recurrence models are completely cured with coloaded BYCs via combination therapy with surgery, utilizing surgically resected tumors as antigens. The BYCs construction and coloading strategy will provide insights and optimistic approaches for the development of effective and controllable cancer vaccine carriers.
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Affiliation(s)
- Guanglei Ma
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Fang Li
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Xin Wang
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Qing Li
- School of Basic Medical Science, Xinxiang Medical University, Xinxiang 453003, P. R. China
| | - Youyou Hong
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Qingcong Wei
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Fangli Gao
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Weiwei Zhang
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Yuming Guo
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Xiaoming Ma
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
| | - Zhiguo Hu
- Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
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Zeting Y, Shuli M, Yue L, Haowei F, Jing S, Yueping Z, Jie W, Teng C, Wanli D, Zhang K, Peihao Y. Tissue adhesive indocyanine green-locking granular gel-mediated photothermal therapy combined with checkpoint inhibitor for preventing postsurgical recurrence and metastasis of colorectal cancer. Bioeng Transl Med 2023; 8:e10576. [PMID: 38023716 PMCID: PMC10658503 DOI: 10.1002/btm2.10576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 06/23/2023] [Accepted: 06/30/2023] [Indexed: 12/01/2023] Open
Abstract
Developing effective therapy to inhibit postoperative recurrence and metastasis of colorectal cancer (CRC) is challenging and significant to reduce mortality and morbidity. Here, a granular hydrogel, assembled from gelatin microgels by dialdehyde starch and interpenetrated with in situ polymerized poly(sulfobetaine methacrylate-co-N-isopropylacrylamide) (P(SBMA-co-NIPAM)), is prepared to load and lock Food and Drug Administration (FDA)-approved indocyanine green (ICG) with definite photothermal function and biosafety for photothermal therapy (PTT) combining with checkpoint inhibitor. The presence of P(SBMA-co-NIPAM) endows granular hydrogel with high retention to water-soluble ICG, preventing easy diffusion and rapid scavenging of ICG. The ICG-locking granular hydrogel can be spread and adhered onto the surgery site at wet state in vivo, exerting a persistent and stable PTT effect. Combined with αPD-L1 treatment, ICG-locking granular hydrogel-mediated PTT can eradicate postsurgery residual and metastatic tumors, and prevent long-term tumor recurrence. Further mechanistic studies indicate that combination treatment effectively promotes dendritic cells maturation in lymph nodes, enhances the number and infiltration of CD8+ T and CD4+ T cells in tumor tissue, and improves memory T cell number in spleen, thus activating the antitumor immune response. Overall, ICG-locking gel-mediated PTT is expected to exhibit broad clinical applications in postoperative treatment of cancers, like CRC.
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Affiliation(s)
- Yuan Zeting
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Central Laboratory, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Department of Pharmaceutics, School of PharmacyEast China University of Science and TechnologyShanghaiChina
- Shanghai Putuo Central School of Clinical MedicineAnhui Medical UniversityHefeiP. R. China
| | - Ma Shuli
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Central Laboratory, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Department of Pharmaceutics, School of PharmacyEast China University of Science and TechnologyShanghaiChina
| | - Li Yue
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Central Laboratory, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
| | - Fang Haowei
- Department of Polymer Materials, School of Materials Science and EngineeringShanghai UniversityShanghaiP. R. China
| | - Shang Jing
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Central Laboratory, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Shanghai Putuo Central School of Clinical MedicineAnhui Medical UniversityHefeiP. R. China
| | - Zhan Yueping
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Central Laboratory, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
| | - Wang Jie
- Department of General Surgery, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
| | - Chen Teng
- Department of General Surgery, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
| | - Deng Wanli
- Department of Oncology, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
| | - Kunxi Zhang
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Department of Polymer Materials, School of Materials Science and EngineeringShanghai UniversityShanghaiP. R. China
| | - Yin Peihao
- Interventional Cancer Institute of Chinese Integrative Medicine & Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
- Department of Pharmaceutics, School of PharmacyEast China University of Science and TechnologyShanghaiChina
- Department of General Surgery, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiP. R. China
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Chen Y, Wu B, Shang H, Sun Y, Tian H, Yang H, Wang C, Wang X, Cheng W. Sono-Immunotherapy Mediated Controllable Composite Nano Fluorescent Probes Reprogram the Immune Microenvironment of Hepatocellular Carcinoma. Int J Nanomedicine 2023; 18:6059-6073. [PMID: 37908671 PMCID: PMC10615103 DOI: 10.2147/ijn.s426297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 10/18/2023] [Indexed: 11/02/2023] Open
Abstract
Background Despite the clinical efficacy of immunotherapy in treating malignant tumors, its effectiveness is often hampered by the immunosuppressive nature of the tumor microenvironment (TME). In this study, we propose the design of a nanoscale ultrasound contrast agent capable of triggering macrophage polarization and immunogenic cell death (ICD) for the treatment of hepatocellular carcinoma (HCC) through sonodynamic treatment (SDT) and immunotherapy. Methods The re-educator (designated as ICG@C3F8-R848 NBs) is composed of the Toll-like receptor agonist resiquimod (R848) and the sonosensitizer Indocyanine green (ICG), utilizing nanobubbles (NBs) as carriers. The technique known as ultrasound-targeted nanobubble destruction (UTND) employs nanosized microbubbles and low-frequency ultrasound (LFUS) to ensure accurate drug delivery and enhance safety. Results Following intravenous delivery, ICG@C3F8-R848 NBs have the potential to selectively target and treat primary tumors using SDT in conjunction with ultrasonography. Importantly, R848 can enhance antitumor immunity by inducing the polarization of macrophages from an M2 to an M1 phenotype. Conclusion The SDT-initiated immunotherapy utilizing ICG@C3F8-R848 NBs demonstrates significant tumor suppression effects with minimal risk of systemic toxicity. The utilization of this self-delivery re-education technique would contribute to advancing the development of nanomedicine for the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Yichi Chen
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Bolin Wu
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Haitao Shang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Yucao Sun
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Huimin Tian
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Huajing Yang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Chunyue Wang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Xiaodong Wang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
| | - Wen Cheng
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China
- Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin, 150081, People’s Republic of China
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Chen XY, Yan MY, Liu Q, Yu BX, Cen Y, Li SY. Chimeric Peptide Engineered Bioregulator for Metastatic Tumor Immunotherapy through Macrophage Polarization and Phagocytosis Restoration. ACS NANO 2023; 17:16056-16068. [PMID: 37578051 DOI: 10.1021/acsnano.3c04778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
Tumor-associated macrophages (TAMs) are the most abundant immune cells in solid tumor tissues, which restrict antitumor immunity by releasing tumor-supporting cytokines and attenuating phagocytosis behaviors. In this work, a chimeric peptide engineered bioregulator (ChiP-RS) is constructed for tumor immunotherapy through macrophage polarization and phagocytosis restoration. ChiP-RS is fabricated by utilizing macrophage-targeting chimeric peptide (ChiP) to load Toll-like receptor agonists (R848) and Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2) inhibitor (SHP099). Among which, ChiP-RS prefers to be internalized by TAMs, repolarizing M2 macrophages into M1 macrophages to reverse the immunosuppressive microenvironment. In addition, SHP-2 can be downregulated to promote phagocytotic elimination behaviors of M1 macrophages, which will also activate T cell-based antitumor immunity for metastatic tumor therapy. In vitro and in vivo findings demonstrate a superior suppression effect of ChiP-RS against metastatic tumors without systemic side effects. Such a simple but effective nanoplatform provides sophisticated synergism for immunotherapy, which may facilitate the development of translational nanomedicine for metastatic tumor treatment.
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Affiliation(s)
- Xia-Yun Chen
- Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
| | - Meng-Yi Yan
- Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
| | - Qianqian Liu
- Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
| | - Bai-Xue Yu
- Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
| | - Yi Cen
- Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
| | - Shi-Ying Li
- Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China
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Qin X, Su M, Guo H, Peng B, Luo R, Ye J, Wang H. Functional biomaterials for the diagnosis and treatment of peritoneal surface malignancies. SMART MEDICINE 2023; 2:e20230013. [PMID: 39188342 PMCID: PMC11235712 DOI: 10.1002/smmd.20230013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 06/03/2023] [Indexed: 08/28/2024]
Abstract
Peritoneal surface malignancies (PSM) can originate from tumors in many organs and are highly malignant, and difficult to diagnose and cure, posing a serious threat to the survival of patients. Although the diagnosis and treatment of PSM have made significant progress in the past two decades, numerous challenges remain. Recently, functionalized biomaterials have shown promise for PSM diagnosis and treatment. Hence, we review the progress of functionalized biomaterials for the diagnosis and treatment of PSM. We first introduce the classification and pathogenesis of PSM. We then discuss the applications of functionalized biomaterials for the diagnosis and treatment of PSM. In particular, we focus on functionalized biomaterials as drug carriers for the treatment of PSM, including chemotherapy, immunotherapy, targeted therapy, combination therapy, and other therapies. Finally, we summarized the current challenges and provided a perspective on the diagnosis and treatment of PSM.
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Affiliation(s)
- Xiusen Qin
- Department of General SurgeryThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesBiomedical Innovation CenterThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Institute of Biomedical Innovation and Laboratory of Regenerative Medicine and BiomaterialsBiomedical Material Conversion and Evaluation Engineering Technology Research Center of Guangdong ProvinceGuangzhouChina
| | - Mingli Su
- Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesBiomedical Innovation CenterThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Department of Endoscopic SurgeryThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Huili Guo
- Department of Infectious DiseasesThe Third Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Binying Peng
- Zhongshan School of MedicineSun Yat‐sen UniversityGuangzhouChina
| | - Rui Luo
- Department of General SurgeryThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesBiomedical Innovation CenterThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Institute of Biomedical Innovation and Laboratory of Regenerative Medicine and BiomaterialsBiomedical Material Conversion and Evaluation Engineering Technology Research Center of Guangdong ProvinceGuangzhouChina
| | - Junwen Ye
- Department of General SurgeryThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesBiomedical Innovation CenterThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Institute of Biomedical Innovation and Laboratory of Regenerative Medicine and BiomaterialsBiomedical Material Conversion and Evaluation Engineering Technology Research Center of Guangdong ProvinceGuangzhouChina
| | - Hui Wang
- Department of General SurgeryThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesBiomedical Innovation CenterThe Sixth Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
- Institute of Biomedical Innovation and Laboratory of Regenerative Medicine and BiomaterialsBiomedical Material Conversion and Evaluation Engineering Technology Research Center of Guangdong ProvinceGuangzhouChina
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Qiu Y, Fan M, Wang Y, Hu X, Chen J, Kamel S, Yang Y, Yang X, Liu H, Zhu Y, Wang Q. Sulfate-reducing bacteria loaded in hydrogel as a long-lasting H 2S factory for tumor therapy. J Control Release 2023; 360:647-659. [PMID: 37406817 DOI: 10.1016/j.jconrel.2023.06.037] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 07/07/2023]
Abstract
The continuous supply of hydrogen sulfide (H2S) gas at high concentrations to tumors is considered a promising and safe strategy for tumor therapy. However, the absence of a durable and cost-effective H2S-producing donor hampers its extensive application. Sulfate-reducing bacteria (SRB) can serve as an excellent H2S factory due to their ability to metabolize sulfate into H2S. Herein, a novel injectable chondroitin sulfate (ChS) hydrogel loaded with SRB (SRB@ChS Gel) is proposed to sustainably produce H2S in tumor tissues to overcome the limitations of current H2S gas therapy. In vitro, the ChS Gel not only supports the growth of encapsulated SRB, but also supplies a sulfate source to the SRB to produce high concentrations of H2S for at least 7 days, resulting in mitochondrial damage and immunogenic cell death. Once injected into tumor tissue, the SRB@ChS Gel can constantly produce H2S for >5 days, significantly inhibiting tumor growth. Furthermore, such treatment activates systemic anti-tumor immune responses, suppresses the growth of distant and recurrent tumors, as well as lung metastases, meanwhile with negligible side effects. Therefore, the injectable SRB@ChS Gel, as a safe and long-term, self-sustained H2S-generating factory, provides a promising strategy for anti-tumor therapy.
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Affiliation(s)
- Yuzhi Qiu
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Man Fan
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Yiqian Wang
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Xiuwen Hu
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Jiawen Chen
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Samir Kamel
- Cellulose and Paper Department, National Research Centre, Dokki, Cairo 12622, Egypt
| | - Yajiang Yang
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Xiangliang Yang
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; National Engineering Research Center for Nanomedicine, Wuhan 430074, China
| | - Hongfang Liu
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Yanhong Zhu
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; National Engineering Research Center for Nanomedicine, Wuhan 430074, China.
| | - Qin Wang
- Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China; National Engineering Research Center for Nanomedicine, Wuhan 430074, China.
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Wang D, Liu J, Duan J, Yi H, Liu J, Song H, Zhang Z, Shi J, Zhang K. Enrichment and sensing tumor cells by embedded immunomodulatory DNA hydrogel to inhibit postoperative tumor recurrence. Nat Commun 2023; 14:4511. [PMID: 37500633 PMCID: PMC10374534 DOI: 10.1038/s41467-023-40085-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 07/10/2023] [Indexed: 07/29/2023] Open
Abstract
Postoperative tumor recurrence and metastases often lead to cancer treatment failure. Here, we develop a local embedded photodynamic immunomodulatory DNA hydrogel for early warning and inhibition of postoperative tumor recurrence. The DNA hydrogel contains PDL1 aptamers that capture and enrich in situ relapsed tumor cells, increasing local ATP concentration to provide a timely warning signal. When a positive signal is detected, local laser irradiation is performed to trigger photodynamic therapy to kill captured tumor cells and release tumor-associated antigens (TAA). In addition, reactive oxygen species break DNA strands in the hydrogel to release encoded PDL1 aptamer and CpG, which together with TAA promote sufficient systemic antitumor immunotherapy. In a murine model where tumor cells are injected at the surgical site to mimic tumor recurrence, we find that the hydrogel system enables timely detection of tumor recurrence by enriching relapsed tumor cells to increase local ATP concentrations. As a result, a significant inhibitory effect of approximately 88.1% on recurrent tumors and effectively suppressing metastasis, offering a promising avenue for timely and effective treatment of postoperative tumor recurrence.
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Affiliation(s)
- Danyu Wang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Jingwen Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Jie Duan
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Hua Yi
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Junjie Liu
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China
| | - Haiwei Song
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
- Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, 138673, Singapore.
| | - Zhenzhong Zhang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China.
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China.
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, 450001, China.
| | - Jinjin Shi
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China.
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China.
| | - Kaixiang Zhang
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
- Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, 450001, China.
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China.
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Kciuk M, Yahya EB, Mohamed Ibrahim Mohamed M, Rashid S, Iqbal MO, Kontek R, Abdulsamad MA, Allaq AA. Recent Advances in Molecular Mechanisms of Cancer Immunotherapy. Cancers (Basel) 2023; 15:2721. [PMID: 37345057 DOI: 10.3390/cancers15102721] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 06/23/2023] Open
Abstract
Cancer is among the current leading causes of death worldwide, despite the novel advances that have been made toward its treatment, it is still considered a major public health concern. Considering both the serious impact of cancer on public health and the significant side effects and complications of conventional therapeutic options, the current strategies towards targeted cancer therapy must be enhanced to avoid undesired toxicity. Cancer immunotherapy has become preferable among researchers in recent years compared to conventional therapeutic options, such as chemotherapy, surgery, and radiotherapy. The understanding of how to control immune checkpoints, develop therapeutic cancer vaccines, genetically modify immune cells as well as enhance the activation of antitumor immune response led to the development of novel cancer treatments. In this review, we address recent advances in cancer immunotherapy molecular mechanisms. Different immunotherapeutic approaches are critically discussed, focusing on the challenges, potential risks, and prospects involving their use.
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Affiliation(s)
- Mateusz Kciuk
- Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
- Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
| | - Esam Bashir Yahya
- Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Penang 11800, Malaysia
| | | | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Muhammad Omer Iqbal
- Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
| | - Renata Kontek
- Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
| | - Muhanad A Abdulsamad
- Department of Molecular Biology, Faculty of Science, Sabratha University, Sabratha 00218, Libya
| | - Abdulmutalib A Allaq
- Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Malaysia
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Kim S, Lee W, Park H, Kim K. Tumor Microenvironment-Responsive 6-Mercaptopurine-Releasing Injectable Hydrogel for Colon Cancer Treatment. Gels 2023; 9:gels9040319. [PMID: 37102931 PMCID: PMC10138092 DOI: 10.3390/gels9040319] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/02/2023] [Accepted: 04/08/2023] [Indexed: 04/28/2023] Open
Abstract
Colon cancer is a significant health concern. The development of effective drug delivery systems is critical for improving treatment outcomes. In this study, we developed a drug delivery system for colon cancer treatment by embedding 6-mercaptopurine (6-MP), an anticancer drug, in a thiolated gelatin/polyethylene glycol diacrylate hydrogel (6MP-GPGel). The 6MP-GPGel continuously released 6-MP, the anticancer drug. The release rate of 6-MP was further accelerated in an acidic or glutathione environment that mimicked a tumor microenvironment. In addition, when pure 6-MP was used for treatment, cancer cells proliferated again from day 5, whereas a continuous supply of 6-MP from the 6MP-GPGel continuously suppressed the survival rate of cancer cells. In conclusion, our study demonstrates that embedding 6-MP in a hydrogel formulation can improve the efficacy of colon cancer treatment and may serve as a promising minimally invasive and localized drug delivery system for future development.
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Affiliation(s)
- Sungjun Kim
- Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul 22012, Republic of Korea
| | - Wonjeong Lee
- Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul 22012, Republic of Korea
| | - Heewon Park
- Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul 22012, Republic of Korea
| | - Kyobum Kim
- Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul 22012, Republic of Korea
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39
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Ren SN, Zhang ZY, Guo RJ, Wang DR, Chen FF, Chen XB, Fang XD. Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer. World J Gastroenterol 2023; 29:1911-1941. [PMID: 37155531 PMCID: PMC10122790 DOI: 10.3748/wjg.v29.i13.1911] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 02/02/2023] [Accepted: 03/21/2023] [Indexed: 04/06/2023] Open
Abstract
Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells’ sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.
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Affiliation(s)
- Sheng-Nan Ren
- Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Zhan-Yi Zhang
- Bethune Third Clinical Medical College, Jilin University, Changchun 130021, Jilin Province, China
| | - Rui-Jie Guo
- Bethune Third Clinical Medical College, Jilin University, Changchun 130021, Jilin Province, China
| | - Da-Ren Wang
- Bethune Third Clinical Medical College, Jilin University, Changchun 130021, Jilin Province, China
| | - Fang-Fang Chen
- Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Xue-Bo Chen
- Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Xue-Dong Fang
- Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
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40
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Desai N, Hasan U, K J, Mani R, Chauhan M, Basu SM, Giri J. Biomaterial-based platforms for modulating immune components against cancer and cancer stem cells. Acta Biomater 2023; 161:1-36. [PMID: 36907233 DOI: 10.1016/j.actbio.2023.03.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 03/02/2023] [Accepted: 03/02/2023] [Indexed: 03/12/2023]
Abstract
Immunotherapy involves the therapeutic alteration of the patient's immune system to identify, target, and eliminate cancer cells. Dendritic cells, macrophages, myeloid-derived suppressor cells, and regulatory T cells make up the tumor microenvironment. In cancer, these immune components (in association with some non-immune cell populations like cancer-associated fibroblasts) are directly altered at a cellular level. By dominating immune cells with molecular cross-talk, cancer cells can proliferate unchecked. Current clinical immunotherapy strategies are limited to conventional adoptive cell therapy or immune checkpoint blockade. Targeting and modulating key immune components presents an effective opportunity. Immunostimulatory drugs are a research hotspot, but their poor pharmacokinetics, low tumor accumulation, and non-specific systemic toxicity limit their use. This review describes the cutting-edge research undertaken in the field of nanotechnology and material science to develop biomaterials-based platforms as effective immunotherapeutics. Various biomaterial types (polymer-based, lipid-based, carbon-based, cell-derived, etc.) and functionalization methodologies for modulating tumor-associated immune/non-immune cells are explored. Additionally, emphasis has been laid on discussing how these platforms can be used against cancer stem cells, a fundamental contributor to chemoresistance, tumor relapse/metastasis, and failure of immunotherapy. Overall, this comprehensive review strives to provide up-to-date information to an audience working at the juncture of biomaterials and cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cancer immunotherapy possesses incredible potential and has successfully transitioned into a clinically lucrative alternative to conventional anti-cancer therapies. With new immunotherapeutics getting rapid clinical approval, fundamental problems associated with the dynamic nature of the immune system (like limited clinical response rates and autoimmunity-related adverse effects) have remained unanswered. In this context, treatment approaches that focus on modulating the compromised immune components within the tumor microenvironment have garnered significant attention amongst the scientific community. This review aims to provide a critical discussion on how various biomaterials (polymer-based, lipid-based, carbon-based, cell-derived, etc.) can be employed along with immunostimulatory agents to design innovative platforms for selective immunotherapy directed against cancer and cancer stem cells.
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Affiliation(s)
- Nimeet Desai
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Uzma Hasan
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India; Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Jeyashree K
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Rajesh Mani
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Meenakshi Chauhan
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Suparna Mercy Basu
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Jyotsnendu Giri
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India.
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Leśniak M, Lipniarska J, Majka P, Kopyt W, Lejman M, Zawitkowska J. The Role of TRL7/8 Agonists in Cancer Therapy, with Special Emphasis on Hematologic Malignancies. Vaccines (Basel) 2023; 11:vaccines11020277. [PMID: 36851155 PMCID: PMC9967151 DOI: 10.3390/vaccines11020277] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/23/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Toll-like receptors (TLR) belong to the pattern recognition receptors (PRR). TLR7 and the closely correlated TLR8 affiliate with toll-like receptors family, are located in endosomes. They recognize single-stranded ribonucleic acid (RNA) molecules and synthetic deoxyribonucleic acid (DNA)/RNA analogs-oligoribonucleotides. TLRs are primarily expressed in hematopoietic cells. There is compiling evidence implying that TLRs also direct the formation of blood cellular components and make a contribution to the pathogenesis of certain hematopoietic malignancies. The latest research shows a positive effect of therapy with TRL agonists on the course of hemato-oncological diseases. Ligands impact activation of antigen-presenting cells which results in production of cytokines, transfer of mentioned cells to the lymphoid tissue and co-stimulatory surface molecules expression required for T-cell activation. Toll-like receptor agonists have already been used in oncology especially in the treatment of dermatological neoplastic lesions. The usage of these substances in the treatment of solid tumors is being investigated. The present review discusses the direct and indirect influence that TLR7/8 agonists, such as imiquimod, imidazoquinolines and resiquimod have on neoplastic cells and their promising role as adjuvants in anticancer vaccines.
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Affiliation(s)
- Maria Leśniak
- Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Justyna Lipniarska
- Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Patrycja Majka
- Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Weronika Kopyt
- Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Monika Lejman
- Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland
| | - Joanna Zawitkowska
- Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland
- Correspondence:
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Gao Y, Wang Z, Cui Y, Xu M, Weng L. Emerging Strategies of Engineering and Tracking Dendritic Cells for Cancer Immunotherapy. ACS APPLIED BIO MATERIALS 2023; 6:24-43. [PMID: 36520013 DOI: 10.1021/acsabm.2c00790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Dendritic cells (DCs), a kind of specialized immune cells, play key roles in antitumor immune response and promotion of innate and adaptive immune responses. Recently, many strategies have been developed to utilize DCs in cancer therapy, such as delivering antigens and adjuvants to DCs and using scaffold to recruit and activate DCs. Here we outline how different DC subsets influence antitumor immunity, summarize the FDA-approved vaccines and cancer vaccines under clinical trials, discuss the strategies for engineering DCs and noninvasive tracking of DCs to improve antitumor immunotherapy, and reveal the potential of artificial neural networks for the design of DC based vaccines.
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Affiliation(s)
- Yu Gao
- State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Zhixuan Wang
- School of Geography and Biological Information, Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Ying Cui
- School of Geography and Biological Information, Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Miaomiao Xu
- School of Geography and Biological Information, Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
| | - Lixing Weng
- State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.,School of Geography and Biological Information, Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China
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43
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Si X, Ji G, Ma S, Chen H, Shi Z, Zhang Y, Tang Z, Song W, Chen X. Comprehensive evaluation of biopolymer immune implants for peritoneal metastasis carcinoma therapy. J Control Release 2023; 353:289-302. [PMID: 36403683 DOI: 10.1016/j.jconrel.2022.11.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 11/03/2022] [Accepted: 11/14/2022] [Indexed: 12/03/2022]
Abstract
Immunotherapy has been widely used in the treatment of advanced stage cancers with spreading metastases, while the fully activation of immune system often requires sustained and long-acting immune stimulation by immunotherapeutic agents. In previous studies, we designed a biopolymer immune implant by dynamic covalent bonds and achieved sustained release of loaded immunotherapeutic agents, thus stimulated systemic immune activation and elicited immune memory effects. Herein, we further optimized the implants and carried out a comprehensive evaluation of the implants on peritoneal metastasis carcinoma (PMC) therapy. Our results showed that the implants fabricated with 8-arm polyethylene glycol amine (8-arm PEG-NH2) and 40% oxidation degree dextran (ODEX) exhibited a satisfactory degradation time for activating the antitumor immunity. The drug combination of oxaliplatin (OxP) and resiquimod (R848) could be sustainably released from the implants for 18 days. The implants cured 75% of mice with PMC and elicited immune memory effects to resist tumor re-challenge without obvious side effects observed. Mechanism analysis revealed that the implants could serve as an in-situ vaccine to enhance the infiltration of activated dendritic cells (DCs), T cells and natural killer (NK) cells inside the tumor, as well as increase the serum tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin 12 (IL-12) levels. These results strongly support the clinical translation potential of this sustained released biopolymer immune implants for PMC therapy.
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Affiliation(s)
- Xinghui Si
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China
| | - Guofeng Ji
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Xuanwu Hospital, Capital Medical University, Beijing 100010, PR China
| | - Sheng Ma
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China
| | - Hongyu Chen
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China
| | - Zhiyuan Shi
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China
| | - Yu Zhang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China
| | - Zhaohui Tang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China
| | - Wantong Song
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.
| | - Xuesi Chen
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.
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Lei L, Huang D, Gao H, He B, Cao J, Peppas NA. Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy. SCIENCE ADVANCES 2022; 8:eadc8738. [PMID: 36427310 PMCID: PMC9699680 DOI: 10.1126/sciadv.adc8738] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 10/07/2022] [Indexed: 05/25/2023]
Abstract
Cancer vaccines have attracted widespread interest in tumor therapy because of the potential to induce an effective antitumor immune response. However, many challenges including weak immunogenicity, off-target effects, and immunosuppressive microenvironments have prevented their broad clinical translation. To overcome these difficulties, effective delivery systems have been designed for cancer vaccines. As carriers in cancer vaccine delivery systems, hydrogels have gained substantial attention because they can encapsulate a variety of antigens/immunomodulators and protect them from degradation. This enables hydrogels to simultaneously reverse immunosuppression and stimulate the immune response. Meanwhile, the controlled release properties of hydrogels allow for precise temporal and spatial release of loads in situ to further enhance the immune response of cancer vaccines. Therefore, this review summarizes the classification of cancer vaccines, highlights the strategies of hydrogel-based cancer vaccines, and provides some insights into the future development of hydrogel-based cancer vaccines.
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Affiliation(s)
- Lei Lei
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China
| | - Dennis Huang
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
- Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA
| | - Huile Gao
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China
| | - Bin He
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China
| | - Jun Cao
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China
| | - Nicholas A. Peppas
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
- Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, TX 78712, USA
- Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
- Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA
- Departments of Pediatrics, Surgery, and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
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Guo Y, Sun L, Wang Y, Wang Q, Jing D, Liu S. Nanomaterials based on thermosensitive polymer in biomedical field. Front Chem 2022; 10:946183. [PMID: 36212064 PMCID: PMC9532752 DOI: 10.3389/fchem.2022.946183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/30/2022] [Indexed: 11/27/2022] Open
Abstract
The progress of nanotechnology enables us to make use of the special properties of materials on the nanoscale and open up many new fields of biomedical research. Among them, thermosensitive nanomaterials stand out in many biomedical fields because of their “intelligent” behavior in response to temperature changes. However, this article mainly reviews the research progress of thermosensitive nanomaterials, which are popular in biomedical applications in recent years. Here, we simply classify the thermally responsive nanomaterials according to the types of polymers, focusing on the mechanisms of action and their advantages and potential. Finally, we deeply investigate the applications of thermosensitive nanomaterials in drug delivery, tissue engineering, sensing analysis, cell culture, 3D printing, and other fields and probe the current challenges and future development prospects of thermosensitive nanomaterials.
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Affiliation(s)
- Yingshu Guo
- Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
- *Correspondence: Yingshu Guo,
| | - Li Sun
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, China
| | - Yajing Wang
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, China
| | - Qianqian Wang
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, China
| | - Dan Jing
- Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Shiwei Liu
- Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
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Bacterial Cellulose as a Versatile Biomaterial for Wound Dressing Application. Molecules 2022; 27:molecules27175580. [PMID: 36080341 PMCID: PMC9458019 DOI: 10.3390/molecules27175580] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/21/2022] [Accepted: 08/26/2022] [Indexed: 12/28/2022] Open
Abstract
Chronic ulcers are among the main causes of morbidity and mortality due to the high probability of infection and sepsis and therefore exert a significant impact on public health resources. Numerous types of dressings are used for the treatment of skin ulcers-each with different advantages and disadvantages. Bacterial cellulose (BC) has received enormous interest in the cosmetic, pharmaceutical, and medical fields due to its biological, physical, and mechanical characteristics, which enable the creation of polymer composites and blends with broad applications. In the medical field, BC was at first used in wound dressings, tissue regeneration, and artificial blood vessels. This material is suitable for treating various skin diseases due its considerable fluid retention and medication loading properties. BC membranes are used as a temporary dressing for skin treatments due to their excellent fit to the body, reduction in pain, and acceleration of epithelial regeneration. BC-based composites and blends have been evaluated and synthesized both in vitro and in vivo to create an ideal microenvironment for wound healing. This review describes different methods of producing and handling BC for use in the medical field and highlights the qualities of BC in detail with emphasis on biomedical reports that demonstrate its utility. Moreover, it gives an account of biomedical applications, especially for tissue engineering and wound dressing materials reported until date. This review also includes patents of BC applied as a wound dressing material.
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Zhang Q, Wang X, Kuang G, Yu Y, Zhao Y. Photopolymerized 3D Printing Scaffolds with Pt(IV) Prodrug Initiator for Postsurgical Tumor Treatment. RESEARCH (WASHINGTON, D.C.) 2022; 2022:9784510. [PMID: 36111316 PMCID: PMC9448443 DOI: 10.34133/2022/9784510] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 08/01/2022] [Indexed: 12/20/2022]
Abstract
Biomedical scaffolds have shown great success in postsurgical tumor treatment; their current efforts are focusing on eradicating residual tumor cells and circulating tumor cells and simultaneously repairing postoperative tissue defects. Herein, we report a novel photopolymerized 3D scaffold with Pt(IV) prodrug initiator to achieve the desired features for tumor comprehensive therapy. The Pt-GelMA scaffold was fabricated from the microfluidic 3D printing of methacrylate gelatin (GelMA) bioinks through a Pt(IV)-induced photocrosslinked process without any other additional photoinitiator and chemotherapeutic drug. Thus, the resultant scaffold displayed efficient cell killing ability against breast cancer cells in vitro and significantly inhibited the local tumor growth and distant metastases on an orthotopic postoperative breast cancer model in vivo. Besides, benefiting from their ordered porous structures and favorable biocompatibility, the scaffolds supported the cell attachment, spreading, and proliferation of normal cells in vitro; could facilitate the nutrient transportation; and induced new tissue ingrowth for repairing tissue defects caused by surgery. These properties indicate that such 3D printing scaffold is a promising candidate for efficient postoperative tumor treatment in the practical application.
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Affiliation(s)
- Qingfei Zhang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Xiaocheng Wang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Gaizhen Kuang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Yunru Yu
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
| | - Yuanjin Zhao
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China
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48
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Inhibition of Colon Cancer Recurrence via Exogenous TRAIL Delivery Using Gel-like Coacervate Microdroplets. Gels 2022; 8:gels8070427. [PMID: 35877512 PMCID: PMC9319433 DOI: 10.3390/gels8070427] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 02/04/2023] Open
Abstract
Colon cancer (CC) belongs to the three major malignancies with a high recurrence rate. Therefore, a novel drug delivery system that can prevent CC recurrence while minimizing side effects is needed. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) has recently been spotlighted as a protein drug that can induce apoptosis of cancer cells specifically. However, its short in vivo half-life is still a challenge to overcome. Hence, in this study, a gel-like mPEGylated coacervate (mPEG-Coa) delivery platform was developed through electrostatic interaction of mPEG-poly(ethylene arginylaspartate diglyceride) (mPEG-PEAD) and heparin for effective protection of cargo TRAIL, subsequently preserving its bioactivity. mPEG-Coa could protect cargo TRAIL against protease. Sustained release was observed for a long-term (14 days). In addition, recurrence of HCT-116 cells was suppressed when cells were treated with TRAIL-loaded mPEG-Coa for 7 days through long-term continuous supply of active TRAIL, whereas re-proliferation occurred in the bolus TRAIL-treated group. Taken together, these results suggest that our gel-like mPEG-Coa could be utilized as a functional delivery platform to suppress CC recurrence by exogenously supplying TRAIL for a long time with a single administration.
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Dang W, Chen WC, Ju E, Xu Y, Li K, Wang H, Wang K, Lv S, Shao D, Tao Y, Li M. 3D printed hydrogel scaffolds combining glutathione depletion-induced ferroptosis and photothermia-augmented chemodynamic therapy for efficiently inhibiting postoperative tumor recurrence. J Nanobiotechnology 2022; 20:266. [PMID: 35672826 PMCID: PMC9171966 DOI: 10.1186/s12951-022-01454-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/05/2022] [Indexed: 12/24/2022] Open
Abstract
AbstractSurgical resection to achieve tumor-free margins represents a difficult clinical scenario for patients with hepatocellular carcinoma. While post-surgical treatments such as chemotherapy and radiotherapy can decrease the risk of cancer recurrence and metastasis, growing concerns about the complications and side effects have promoted the development of implantable systems for locoregional treatment. Herein, 3D printed hydrogel scaffolds (designed as Gel-SA-CuO) were developed by incorporating one agent with multifunctional performance into implantable devices to simplify the fabrication process for efficiently inhibiting postoperative tumor recurrence. CuO nanoparticles can be effectively controlled and sustained released during the biodegradation of hydrogel scaffolds. Notably, the released CuO nanoparticles not only function as the reservoir for releasing Cu2+ to produce intracellular reactive oxygen species (ROS) but also serve as photothermal agent to generate heat. Remarkably, the heat generated by photothermal conversion of CuO nanoparticles further promotes the efficiency of Fenton-like reaction. Additionally, ferroptosis can be induced through Cu2+-mediated GSH depletion via the inactivation of GPX4. By implanting hydrogel scaffolds in the resection site, efficient inhibition of tumor recurrence after primary resection can be achieved in vivo. Therefore, this study may pave the way for the development of advanced multifunctional implantable platform for eliminating postoperative relapsable cancers.
Graphical Abstract
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50
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Gao Y, Zhao J, Huang Z, Zhao H, Guo Z, Ma S, Tang X, Song W, Chen X. In Situ Reprogramming of Tumors for Activating the OX40/OX40 Ligand Checkpoint Pathway and Boosting Antitumor Immunity. ACS Biomater Sci Eng 2022. [PMID: 35653749 DOI: 10.1021/acsbiomaterials.1c01637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OX40 (CD134, TNFRSF4) is a member of the tumor necrosis factor receptor superfamily that can be activated by its cognate ligand OX40L (CD252, TNFSF4) and functions as a pair of T cell costimulatory molecules. The interaction between OX40 and OX40L (OX40/OX40L) plays a critical role in regulating antitumor immunity, including promoting effector T cells expansion and survival, blocking natural regulatory T cells (Treg) activity, and antagonizing inducible Treg generation. However, current OX40 agonists including anti-OX40 monoclonal antibodies (aOX40) have serious side effects after systemic administration, which limits their clinical success and application. Herein, we propose a strategy to reprogram tumor cells into OX40L-expressing "artificial" antigen-presenting cells (APCs) by OX40L plasmid-loaded nanoparticles for boosting antitumor immunity in situ. A novel gene transfection carrier was prepared by a modular hierarchical assembly method, which could efficiently transfect various tumor cells and express OX40L proteins on their surface. These surface-decorated OX40L proteins were proved to stimulate T cell proliferation in vitro while stimulating strong antitumor immune responses in vivo. Importantly, this in situ reprogramming strategy did not induce any toxicity as observed in aOX40 treatment, thus providing a novel method for immune checkpoint stimulator application.
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Affiliation(s)
- Yuxi Gao
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.,Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
| | - Jiayu Zhao
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,University of Science and Technology of China, Hefei 230026, China
| | - Zichao Huang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,University of Science and Technology of China, Hefei 230026, China
| | - Hanqin Zhao
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,University of Science and Technology of China, Hefei 230026, China
| | - Zhaopei Guo
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Sheng Ma
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Xing Tang
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Wantong Song
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Xuesi Chen
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.,University of Science and Technology of China, Hefei 230026, China.,Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
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