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Liu X, Zhang H, Guan S, Tan J, Yeung KWK, Ouyang L, Liu X. Electron Pump and Photon Trap Effect-Derived Selective Antitumor of Fe-Ppy@CaO 2-Modified Polyetheretherketone for Bone Tumor Therapy. ACS NANO 2025; 19:14954-14971. [PMID: 40197016 DOI: 10.1021/acsnano.5c00721] [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: 04/09/2025]
Abstract
Bone tumors with high mortality and disability have become a major clinical challenge. Herewith, it is necessary to design materials for bone tumor therapy and bone repair. In this work, Fe-doped polypyrrole (Fe-Ppy) and CaO2 are constructed on sulfonated polyetheretherketone (SP) to form a multistage-responsive coating. The coating achieves long-lasting antitumor through chemodynamic therapy (CDT), photothermal therapy (PTT), and combined immunotherapy. Fe-Ppy acts as an electron pump to replenish Fe2+ through oxidizing -NH- to -N+-, which lasts the Fenton reaction and persistently produces reactive oxygen species (ROS) in the tumor microenvironment (TME). CaO2 selectively provides exogenous H2O2 in response to TME to boost the electron cycle. Stronger near-infrared light absorption due to Fe doping and more photon traps caused by porous structure-induced scattering and refraction diminishment improve the photothermal conversion of modified SP. Furthermore, long-lasting ROS and effective photothermal conversion enhance M1 activation to secrete TNF-α and IFN to kill tumor cells. After tumor therapy, Fe-Ppy@CaO2-modified SP could adaptively switch the macrophage to M2 and promote osteogenesis with the abolishment of TME and NIR stimulation. In summary, Fe-Ppy@CaO2-modified SP with long-lasting ROS, enhanced photothermal conversion, and immunomodulation is a potential candidate for bone tumor therapy and tissue repair.
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Affiliation(s)
- Xingdan Liu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
- Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai 200336, China
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
| | - Haifeng Zhang
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
- School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China
| | - Shiwei Guan
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
| | - Ji Tan
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
| | - Kelvin W K Yeung
- Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, Guangdong Engineering Technology Research Center for Orthopaedic Trauma Repair, Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Liping Ouyang
- Shanghai Key Laboratory of Flexible Medical Robotics, Tongren Hospital, Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai 200336, China
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
| | - Xuanyong Liu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
- School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China
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2
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Zhang L, Wang S, Hou Y. Magnetic Micro/nanorobots in Cancer Theranostics: From Designed Fabrication to Diverse Applications. ACS NANO 2025; 19:7444-7481. [PMID: 39970007 DOI: 10.1021/acsnano.4c10382] [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: 02/21/2025]
Abstract
Cancer poses a substantial threat and a serious challenge to public human health, driving the promotion of sophisticated technologies for cancer therapy. While conventional chemotherapy has bottlenecks such as low delivery efficiency, strong toxic side effects, and tumor enrichment barriers, magnetic micro/nanorobots (MNRs) emerge as promising therapeutic candidates that provide alternative strategies for cancer therapy. MNR is a kind of human-made machine that is micro- or nanosized, is reasonably designed, and performs command tasks through self-actuated or externally controlled propulsion mechanisms, which can be potentially applied in cancer theranostics. Here, this review first introduces the components that constitute a typical magnetic MNR, including the body part, the driving part, the control part, the function part, and the sensing part. Subsequently, this review elucidates representative fabrication methods to construct magnetic MNRs from top-down approaches to bottom-up approaches, covering injection molding, self-rolling, melt electrospinning writing, deposition, biotemplate method, lithography, assembling, 3D printing, and chemical synthesis. Furthermore, this review focuses on multiple applications of magnetic MNRs facing cancer diagnosis and treatment, encompassing imaging, quantification, drug release, synergy with typical therapies, cell manipulation, and surgical assistance. Then, this review systematically elaborates on the biocompatibility and biosafety of magnetic MNRs. Finally, the challenges faced by magnetic MNRs are discussed alongside future research directions. This review is intended to provide scientific guidance that may improve the comprehension and cognition of cancer theranostics through the platform of magnetic MNRs, promoting and prospering the practical application development of magnetic MNRs.
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Affiliation(s)
- Lin Zhang
- Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Shuren Wang
- Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Yanglong Hou
- Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing 100871, China
- School of Materials, Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
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3
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Wang X, Wei N, Zhang Y, Fang Y, Li Y, Li S, Wang Z, Sun C. Nanozyme-mediated glutathione depletion for enhanced ROS-based cancer therapies: a comprehensive review. Nanomedicine (Lond) 2025; 20:279-290. [PMID: 39726369 PMCID: PMC11792818 DOI: 10.1080/17435889.2024.2446138] [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: 10/28/2024] [Accepted: 12/20/2024] [Indexed: 12/28/2024] Open
Abstract
Nanozymes can improve reactive oxygen species (ROS)-based cancer therapies by targeting cancer cells' antioxidant defense mechanisms, particularly glutathione (GSH) depletion, to overcome ROS-resistant cancer cells. Nanozymes, innovative enzyme-mimetic nanomaterials, can generate ROS, alter the tumor microenvironment (TME), and synergize with photodynamic therapy (PDT), chemodynamic therapy (CDT), radiotherapy, and immunotherapy. This review shows how nanozymes catalyze ROS generation, selectively deplete GSH, and target cancer elimination, offering clear advantages over standard therapies. Nanozymes selectively target cancer cells' antioxidant defenses to improve PDT, CDT, and radiation therapies. To maximize nanozyme-based cancer treatment efficacy, biodistribution, biocompatibility, and tumor heterogeneity must be assessed. To improve cancer treatment, multifunctional, stimuli-responsive nanozymes and synergistic combination drugs should be developed.
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Affiliation(s)
- Xinyu Wang
- School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, People’s Republic of China
| | - Nan Wei
- Department of radiotherapy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, people’s Republic of China
| | - Yang Zhang
- Department of radiotherapy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, people’s Republic of China
| | - Yuan Fang
- Department of radiotherapy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, people’s Republic of China
| | - Yijun Li
- Department of Pathology, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, People’s Republic of China
| | - Songguo Li
- Department of Pathology, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, People’s Republic of China
| | - Zhanggui Wang
- Department of radiotherapy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, people’s Republic of China
| | - Chenglong Sun
- Department of radiotherapy, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, people’s Republic of China
- Department of radiotherapy, Anhui No.2 Provincial People’s Hospital Clinical College, Anhui Medical University, Hefei, Anhui, People’s Republic of China
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4
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Cai W, Sun T, Qiu C, Sheng H, Chen R, Xie C, Kou L, Yao Q. Stable triangle: nanomedicine-based synergistic application of phototherapy and immunotherapy for tumor treatment. J Nanobiotechnology 2024; 22:635. [PMID: 39420366 PMCID: PMC11488210 DOI: 10.1186/s12951-024-02925-3] [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: 10/03/2023] [Accepted: 10/10/2024] [Indexed: 10/19/2024] Open
Abstract
In recent decades, cancer has posed a challenging obstacle that humans strive to overcome. While phototherapy and immunotherapy are two emerging therapies compared to traditional methods, they each have their advantages and limitations. These limitations include easy metastasis and recurrence, low response rates, and strong side effects. To address these issues, researchers have increasingly focused on combining these two therapies by utilizing a nano-drug delivery system due to its superior targeting effect and high drug loading rate, yielding remarkable results. The combination therapy demonstrates enhanced response efficiency and effectiveness, leading to a preparation that is highly targeted, responsive, and with low recurrence rates. This paper reviews several main mechanisms of anti-tumor effects observed in combination therapy based on the nano-drug delivery system over the last five years. Furthermore, the challenges and future prospects of this combination therapy are also discussed.
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Affiliation(s)
- Wenjing Cai
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China
| | - Tuyue Sun
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Chenyu Qiu
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China
| | - Huixiang Sheng
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Ruijie Chen
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China
| | - Congying Xie
- Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, Wenzhou, 325000, China.
- Zhejiang-Hong Kong Precision Theranostics of Thoracic Tumors Joint Laboratory, Wenzhou, 325000, China.
| | - Longfa Kou
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
- Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China.
- Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, Wenzhou, 325000, China.
- Zhejiang-Hong Kong Precision Theranostics of Thoracic Tumors Joint Laboratory, Wenzhou, 325000, China.
| | - Qing Yao
- Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
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5
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Sancho-Albero M, Fenaroli AL, Scaccaglia M, Matteo C, Grasselli C, Zucchetti M, Frapolli R, Nastasi C, De Cola L. Two Different Responsive Organosilica Nanocarriers to Combine Chemo- and Immunotherapy against Cancer. ACS OMEGA 2024; 9:41225-41235. [PMID: 39398182 PMCID: PMC11465578 DOI: 10.1021/acsomega.4c02838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 07/22/2024] [Accepted: 08/08/2024] [Indexed: 10/15/2024]
Abstract
The combination of chemo- and immunotherapy was recently demonstrated to improve a patient's response to therapy, giving rise to an emerging cancer treatment known as chemoimmunotherapy (CIT). Despite the promising benefits of CIT, the most important challenges are (i) the simultaneous or time-controlled delivery of two drugs and (ii) the selective uptake into different cells for each of the drugs: cancer cells for the chemotherapeutic and macrophages for the immunostimulation actives. Herein, a delivery strategy based on morphologically different stimuli-responsive breakable organosilica nanocarriers is exploited to transport two distinct drugs in the different cells using different times of delivery. We employ stimulus-sensitive, PEGylated organosilica nanocages to encapsulate the chemotherapeutic agent doxorubicin, which is preferentially taken up by tumor cells vs macrophages. On the other hand, similar size mesoporous organosilica nanoparticles, preferentially internalized by macrophages, are filled with the immunostimulator resiquimod. The administration in a sequential manner of the two different nanocarriers allowed us to assess the integrated effect of the combined therapy versus treatment with a single drug. In vitro work clearly shows an important reduction of tumor cell viability when both chemo- and immunotherapeutic agents are delivered.
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Affiliation(s)
- Maria Sancho-Albero
- Department
of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Alessia Lucrezia Fenaroli
- Department
of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Mirco Scaccaglia
- Department
of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Cristina Matteo
- Department
of Oncology, Laboratory of Cancer Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Chiara Grasselli
- Department
of Oncology, Immunopharmacology Unit, Istituto
di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Massimo Zucchetti
- Department
of Oncology, Laboratory of Cancer Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Roberta Frapolli
- Department
of Oncology, Laboratory of Cancer Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Claudia Nastasi
- Department
of Oncology, Immunopharmacology Unit, Istituto
di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
| | - Luisa De Cola
- Department
of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan 20156, Italy
- Department
of Pharmaceutical Science, DISFARM, Università
degli Studi di Milano, Milan 20133, Italy
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6
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Xu X, Zhang Y, Meng C, Zheng W, Wang L, Zhao C, Luo F. Nanozymes in cancer immunotherapy: metabolic disruption and therapeutic synergy. J Mater Chem B 2024; 12:9111-9143. [PMID: 39177061 DOI: 10.1039/d4tb00769g] [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: 08/24/2024]
Abstract
Over the past decade, there has been a growing emphasis on investigating the role of immunotherapy in cancer treatment. However, it faces challenges such as limited efficacy, a diminished response rate, and serious adverse effects. Nanozymes, a subset of nanomaterials, demonstrate boundless potential in cancer catalytic therapy for their tunable activity, enhanced stability, and cost-effectiveness. By selectively targeting the metabolic vulnerabilities of tumors, they can effectively intensify the destruction of tumor cells and promote the release of antigenic substances, thereby eliciting immune clearance responses and impeding tumor progression. Combined with other therapies, they synergistically enhance the efficacy of immunotherapy. Hence, a large number of metabolism-regulating nanozymes with synergistic immunotherapeutic effects have been developed. This review summarizes recent advancements in cancer immunotherapy facilitated by nanozymes, focusing on engineering nanozymes to potentiate antitumor immune responses by disturbing tumor metabolism and performing synergistic treatment. The challenges and prospects in this field are outlined. We aim to provide guidance for nanozyme-mediated immunotherapy and pave the way for achieving durable tumor eradication.
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Affiliation(s)
- Xiangrui Xu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yaowen Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Chijun Meng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Wenzhuo Zheng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Lingfeng Wang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Chenyi Zhao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Feng Luo
- Department of Prosthodontics, West China School of Stomatology, Sichuan University, No. 14, Section 3, Renmin Nanlu, Chengdu 610041, China.
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7
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Wang Z, Wang J, Xu W, Qiao L, Xie Y, Gao M, Wang D, Li C. Fasting-Mimicking Diet Facilitates Anti-tumor Therapeutic Effects by Nutrient-Sensitive Nanocomposites. Adv Healthc Mater 2024; 13:e2400943. [PMID: 38856967 DOI: 10.1002/adhm.202400943] [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: 03/12/2024] [Revised: 06/07/2024] [Indexed: 06/11/2024]
Abstract
Cancer cells support their uncontrolled proliferation primarily by regulating energy metabolism. Inhibiting tumor growth by blocking the supply of nutrients is an effective treatment strategy. Fasting-mimicking diet (FMD), as a low-calorie, low-protein, low-sugar, high-fat diet, can effectively reduce the nutrient supply to tumor cells. However, the significant biological barrier presented by the tumor microenvironment imposes greater demands and challenges for drug design. This study constructs the multifunctional nanocomposite ZnFe2O4@TiO2@CHC@Orl-FA (ZTCOF), which has great potential to overcome the aforementioned drawbacks. ZnFe2O4@TiO2 could produce 1O2 with ultrasound, and stimulate the Fenton-like conversion of endogenous H2O2 to ·OH, achieving a combined therapeutic effect of sonodynamic therapy (SDT) and chemodynamic therapy (CDT). Orl (Orlistat) and CHC (α-cyano-4-hydroxycinnamic acid) not only block tumor cell energy metabolism but also increase sensitivity to reactive oxygen species, enhancing the cytotoxic effect on tumor cells. Furthermore, combining the treatment strategies with FMD condition control can further inhibit cancer cell energy metabolism, achieving significant synergistic anti-tumor therapy. Both in vitro and in vivo experiments confirm that ZTCOF with SDT/CDT/starvation can achieve effective tumor suppression and destruction. This work provides theoretical and technical support for anti-tumor multimodal synergistic therapy.
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Affiliation(s)
- Zhifang Wang
- Shenzhen Research Institute of Shandong University, Shenzhen, 518057, China
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
| | - Junrong Wang
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
| | - Wencheng Xu
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
| | - Luying Qiao
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
| | - Yulin Xie
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
| | - Minghong Gao
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
| | - Dongmei Wang
- Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Sciences, Zhejiang Normal University, Jinhua, 321004, P. R. China
| | - Chunxia Li
- Shenzhen Research Institute of Shandong University, Shenzhen, 518057, China
- Institute of Frontier Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Qingdao, Shandong, 266237, China
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8
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Zhou Y, Zhou XX, Jiang H, Liu W, Chen F, Gardea-Torresdey JL, Yan B. In Vitro Toxicity and Modeling Reveal Nanoplastic Effects on Marine Bivalves. ACS NANO 2024; 18:17228-17239. [PMID: 38877988 DOI: 10.1021/acsnano.4c04607] [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: 07/03/2024]
Abstract
Nanoplastics (NPs) represent a growing concern for global environmental health, particularly in marine ecosystems where they predominantly accumulate. The impact of NPs on marine benthic organisms, such as bivalves, raises critical questions regarding ecological integrity and food safety. Traditional methods for assessing NP toxicity are often limited by their time-intensive nature and ethical considerations. Herein, we explore the toxicological effects of NPs on the marine bivalve Ruditapes philippinarum, employing a combination of in vitro cellular assays and advanced modeling techniques. Results indicate a range of adverse effects at the organismal level, including growth inhibition (69.5-108%), oxidative stress, lipid peroxidation, and DNA damage in bivalves, following exposure to NPs at concentrations in the range of 1.6 × 109-1.6 × 1011 particles/mL (p/mL). Interestingly, the growth inhibition predicted by models (54.7-104%), based on in vitro cellular proliferation assays, shows strong agreement with the in vivo outcomes of NP exposure. Furthermore, we establish a clear correlation between cytotoxicity observed in vitro and the toxicological responses at the organismal level. Taken together, this work suggests that the integration of computational modeling with in vitro toxicity assays can predict the detrimental effects of NPs on bivalves, offering insightful references for assessing the environmental risk assessment of NPs in marine benthic ecosystems.
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Affiliation(s)
- Yanfei Zhou
- Institute of Environmental Research at the Greater Bay Area, Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou 510006, China
| | - Xiao-Xia Zhou
- National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-Environmental Pollution Control and Management, Institute of Eco-Environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou 510650, China
| | - Hao Jiang
- CAS Key Laboratory of Aquatic Botany and Watershed Ecology, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China
| | - Wenzhi Liu
- CAS Key Laboratory of Aquatic Botany and Watershed Ecology, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China
| | - Fengyuan Chen
- Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China
| | - Jorge L Gardea-Torresdey
- Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, Texas 79968, United States
| | - Bing Yan
- Institute of Environmental Research at the Greater Bay Area, Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou 510006, China
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9
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Sun H, Bai Y, Zhao D, Wang J, Qiu L. Transition-Metal-Oxide-Based Nanozymes for Antitumor Applications. MATERIALS (BASEL, SWITZERLAND) 2024; 17:2896. [PMID: 38930266 PMCID: PMC11205014 DOI: 10.3390/ma17122896] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/19/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024]
Abstract
Transition metal oxide (TMO)-based nanozymes have appeared as hopeful tools for antitumor applications due to their unique catalytic properties and ability to modulate the tumor microenvironment (TME). The purpose of this review is to provide an overview of the latest progress made in the field of TMO-based nanozymes, focusing on their enzymatic activities and participating metal ions. These nanozymes exhibit catalase (CAT)-, peroxidase (POD)-, superoxide dismutase (SOD)-, oxidase (OXD)-, and glutathione oxidase (GSH-OXD)-like activities, enabling them to regulate reactive oxygen species (ROS) levels and glutathione (GSH) concentrations within the TME. Widely studied transition metals in TMO-based nanozymes include Fe, Mn, Cu, Ce, and the hybrid multimetallic oxides, which are also summarized. The review highlights several innovative nanozyme designs and their multifunctional capabilities. Despite the significant progress in TMO-based nanozymes, challenges such as long-term biosafety, targeting precision, catalytic mechanisms, and theoretical supports remain to be addressed, and these are also discussed. This review contributes to the summary and understanding of the rapid development of TMO-based nanozymes, which holds great promise for advancing nanomedicine and improving cancer treatment.
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Affiliation(s)
| | | | | | - Jianhao Wang
- School of Pharmacy, Changzhou University, Changzhou 213164, China
| | - Lin Qiu
- School of Pharmacy, Changzhou University, Changzhou 213164, China
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10
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Li X, Lin G, Zhou L, Prosser O, Malakooti MH, Zhang M. Green synthesis of iron-doped graphene quantum dots: an efficient nanozyme for glucose sensing. NANOSCALE HORIZONS 2024; 9:976-989. [PMID: 38568029 DOI: 10.1039/d4nh00024b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2024]
Abstract
Single-atom nanozymes with well-defined atomic structures and electronic coordination environments can effectively mimic the functions of natural enzymes. However, the costly and intricate preparation processes have hindered further exploration and application of these single-atom nanozymes. In this study, we presented a synthesis technique for creating Fe-N central single-atom doped graphene quantum dot (FeN/GQDs) nanozymes using a one-step solvothermal process, where individual iron atoms form strong bonds with graphene quantum dots through nitrogen coordination. Unlike previous studies, this method significantly simplifies the synthesis conditions for single-atom nanozymes, eliminating the need for high temperatures and employing environmentally friendly precursors derived from pineapple (ananas comosus) leaves. The resulting FeN/GQDs exhibited peroxidase-like catalytic activity and kinetics comparable to that of natural enzymes, efficiently converting H2O2 into hydroxyl radical species. Leveraging their excellent peroxide-like activity, FeN/GQDs nanozymes have been successfully applied to construct a colorimetric biosensor system characterized by remarkably high sensitivity for glucose detection. This achievement demonstrated a promising approach to designing single-atom nanozymes with both facile synthesis procedures and high catalytic activity, offering potential applications in wearable sensors and personalized health monitoring.
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Affiliation(s)
- Xinqi Li
- Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
| | - Guanyou Lin
- Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
| | - Lijun Zhou
- Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
| | - Octavia Prosser
- Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
| | - Mohammad H Malakooti
- Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
- Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
- Institute for Nano-Engineered Systems, University of Washington, Seattle, WA 98195, USA
| | - Miqin Zhang
- Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195, USA.
- Institute for Nano-Engineered Systems, University of Washington, Seattle, WA 98195, USA
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11
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Chen KD, Wang KL, Chen C, Zhu YJ, Tang WW, Wang YJ, Chen ZP, He LH, Chen YG, Zhang W. Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway. World J Gastroenterol 2024; 30:2709-2725. [PMID: 38855154 PMCID: PMC11154682 DOI: 10.3748/wjg.v30.i20.2709] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 04/18/2024] [Accepted: 05/07/2024] [Indexed: 05/27/2024] Open
Abstract
BACKGROUND Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.
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Affiliation(s)
- Kai-Di Chen
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Kui-Ling Wang
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Chen Chen
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yi-Jia Zhu
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Wen-Wen Tang
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yu-Ji Wang
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Ze-Peng Chen
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Lin-Hai He
- Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- The No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Yu-Gen Chen
- Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
- Jiangsu Collaborative Innovation Center of Chinese Medicine in Prevention and Treatment of Tumor, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
| | - Wei Zhang
- Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
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12
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Ouyang R, Huang Y, Ma Y, Feng M, Liu X, Geng C, Zhao Y, Zhou S, Liu B, Miao Y. Nanomaterials promote the fast development of electrochemical MiRNA biosensors. RSC Adv 2024; 14:17929-17944. [PMID: 38836170 PMCID: PMC11149695 DOI: 10.1039/d3ra08258j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 05/18/2024] [Indexed: 06/06/2024] Open
Abstract
Cancer has become the leading cause of death worldwide. In recent years, molecular diagnosis has demonstrated great potential in the prediction and diagnosis of cancer. MicroRNAs (miRNAs) are short oligonucleotides that regulate gene expression and cell function and are considered ideal biomarkers for cancer detection, diagnosis, and patient prognosis. Therefore, the specific and sensitive detection of ultra-low quantities of miRNA is of great significance. MiRNA biosensors based on electrochemical technology have advantages of high sensitivity, low cost and fast response. Nanomaterials show great potential in miRNA electrochemical detection and promote the rapid development of electrochemical miRNA biosensors. Some methods and signal amplification strategies for miRNA detection in recent years are reviewed herein, followed by a discussion of the latest progress in electrochemical miRNA detection based on different types of nanomaterial. Future perspectives and challenges are also proposed for further exploration of nanomaterials to bring breakthroughs in electrochemical miRNA detection.
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Affiliation(s)
- Ruizhuo Ouyang
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Ying Huang
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Yuanhui Ma
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Meina Feng
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Xi Liu
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Chongrui Geng
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Yuefeng Zhao
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Shuang Zhou
- Cancer Institute, Tongji University School of Medicine Shanghai 200093 China
| | - Baolin Liu
- School of Health Science and Engineering, University of Shanghai for Science and Technology Shanghai 200093 China
| | - Yuqing Miao
- Institute of Bismuth and Rhenium Science, University of Shanghai for Science and Technology Shanghai 200093 China
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13
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Shahnazarova G, Al Hoda Al Bast N, Ramirez JC, Nogues J, Esteve J, Fraxedas J, Serra A, Esplandiu MJ, Sepulveda B. Fe/Au galvanic nanocells to generate self-sustained Fenton reactions without additives at neutral pH. MATERIALS HORIZONS 2024; 11:2206-2216. [PMID: 38415289 DOI: 10.1039/d3mh01935g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
The generation of reactive oxygen species (ROS) via the Fenton reaction has received significant attention for widespread applications. This reaction can be triggered by zero-valent metal nanoparticles by converting externally added H2O2 into hydroxyl radicals (˙OH) in acidic media. To avoid the addition of external additives or energy supply, developing self-sustained catalytic systems enabling onsite production of H2O2 at a neutral pH is crucial. Here, we present novel galvanic nanocells (GNCs) based on metallic Fe/Au bilayers on arrays of nanoporous silica nanostructures for the generation of self-sustained Fenton reactions. These GNCs exploit the large electrochemical potential difference between the Fe and Au layers to enable direct H2O2 production and efficient release of Fe2+ in water at neutral pH, thereby triggering the Fenton reaction. Additionally, the GNCs promote Fe2+/Fe3+ circulation and minimize side reactions that passivate the iron surface to enhance their reactivity. The capability to directly trigger the Fenton reaction in water at pH 7 is demonstrated by the fast degradation and mineralization of organic pollutants, by using tiny amounts of catalyst. The self-generated H2O2 and its transformation into ˙OH in a neutral environment provide a promising route not only in environmental remediation but also to produce therapeutic ROS and address the limitations of Fenton catalytic nanostructures.
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Affiliation(s)
- Gubakhanim Shahnazarova
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, E-08193 Barcelona, Spain.
- Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain
| | - Nour Al Hoda Al Bast
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, E-08193 Barcelona, Spain.
- Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain
| | - Jessica C Ramirez
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, E-08193 Barcelona, Spain.
- Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain
| | - Josep Nogues
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, E-08193 Barcelona, Spain.
- ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain
| | - Jaume Esteve
- Instituto de Microelectrónica de Barcelona (IMB-CNM, CSIC), Barcelona, 08193, Spain.
| | - Jordi Fraxedas
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, E-08193 Barcelona, Spain.
| | - Albert Serra
- Grup d'Electrodeposició de Capes Primes i Nanoestructures (GE-CPN), Departament de Ciència de Materials i Química Física, Universitat de Barcelona, Martí i Franquès, 1, E-08028, Barcelona, Catalonia, Spain
- Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Maria J Esplandiu
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, E-08193 Barcelona, Spain.
| | - Borja Sepulveda
- Instituto de Microelectrónica de Barcelona (IMB-CNM, CSIC), Barcelona, 08193, Spain.
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14
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Wang S, Hou Y. New Types of Magnetic Nanoparticles for Stimuli-Responsive Theranostic Nanoplatforms. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2305459. [PMID: 37988692 PMCID: PMC10885654 DOI: 10.1002/advs.202305459] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/21/2023] [Indexed: 11/23/2023]
Abstract
Magnetic nanomaterials have played a crucial role in promoting the application of nanotechnology in the biomedical field. Although conventional magnetic nanomaterials such as iron oxide nanoparticles (NPs) are used as biosensors, drug delivery vehicles, diagnostic and treatment agents for several diseases, the persistent pursuit of high-performance technologies has prompted researchers to continuously develop new types of magnetic nanomaterials such as iron carbide NPs. Considering their potential application in biomedicine, magnetic NPs responsive to exogenous or endogenous stimuli are developed, thereby enhancing their applicability in more complex versatile scenarios. In this review, the synthesis and surface modification of magnetic NPs are focused, particularly iron carbide NPs. Subsequently, exogenous and endogenous stimuli-responsive magnetic NP-based theranostic platforms are introduced, particularly focusing on nanozyme-based technologies and magnetic NP-mediated immunotherapy, which are emerging stimuli-responsive treatments. Finally, the challenges and perspectives of magnetic NPs to accelerate future research in this field are discussed.
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Affiliation(s)
- Shuren Wang
- Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Yanglong Hou
- Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing, 100871, China
- School of Materials, Sun Yat-Sen University, Shenzhen, 518107, China
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15
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Li K, Xu K, Liu S, He Y, Tan M, Mao Y, Yang Y, Wu J, Feng Q, Luo Z, Cai K. All-in-One Engineering Multifunctional Nanoplatforms for Sensitizing Tumor Low-Temperature Photothermal Therapy In Vivo. ACS NANO 2023; 17:20218-20236. [PMID: 37838975 DOI: 10.1021/acsnano.3c05991] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2023]
Abstract
Low-temperature photothermal therapy (PTT) is a noninvasive method that harnesses the photothermal effect at low temperatures to selectively eliminate tumor cells, while safeguarding normal tissues, minimizing thermal damage, and enhancing treatment safety. First we evaluated the transcriptome of tumor cells at the gene level following low-temperature treatment and observed significant enrichment of genes involved in cell cycle and heat response-related signaling pathways. To address this challenge, we have developed an engineering multifunctional nanoplatform that offered an all-in-one strategy for efficient sensitization of low-temperature PTT. Specifically, we utilized MoS2 nanoparticles as the photothermal core to generate low temperature (40-48 °C). The nanoplatform was coated with DPA to load CPT-11 and Fe2+ and was further modified with PEG and iRGD to enhance tumor specificity (MoS2/Fe@CPT-11-PEG-iRGD). Laser- and acid-triggered release of CPT-11 can significantly increase intracellular H2O2 content, cooperate with Fe2+ ions to increase intracellular lipid ROS content, and activate ferroptosis. Furthermore, CPT-11 induced cell cycle arrest in the temperature-sensitive S-phase, and increased lipid ROS levels contributed to the degradation of HSPs protein expression. This synergistic approach could effectively induce tumor cell death by the sensitized low-temperature PTT and the combination of ferroptosis and chemotherapy. Our nanoplatform can also maximize tumor cell eradication and prolong the survival time of tumor-bearing mice in vivo. The multifunctional approach will provide more possibilities for clinical applications of low-temperature PTT and potential avenues for the development of multiple tumor treatments.
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Affiliation(s)
- Ke Li
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
- Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina 27708, United States
| | - Kun Xu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Shaopeng Liu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Ye He
- Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina 27708, United States
| | - Meijun Tan
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Yulan Mao
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Yulu Yang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Jing Wu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Qian Feng
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
| | - Zhong Luo
- School of Life Science, Chongqing University, Chongqing 400044, P. R. China
| | - Kaiyong Cai
- Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China
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16
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Feng H, Zhao Y, Li Y, Qi X, Shen S, Zhou S. Multi-Armed Anti-CD40-Mediated Dual Drug Delivery System Based on Mesoporous Silica/Au Nanorod Nanocomposites for Multimodality Imaging and Combination Therapy. ACS APPLIED NANO MATERIALS 2023; 6:13001-13012. [DOI: 10.1021/acsanm.3c01722] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/26/2024]
Affiliation(s)
- Honghong Feng
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China
| | - Yangjing Zhao
- Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, P. R. China
| | - Yeping Li
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China
| | - Xueyong Qi
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China
| | - Song Shen
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China
| | - Shengwang Zhou
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China
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17
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Jiang H, Fu H, Min T, Hu P, Shi J. Magnetic-Manipulated NK Cell Proliferation and Activation Enhance Immunotherapy of Orthotopic Liver Cancer. J Am Chem Soc 2023. [PMID: 37262421 DOI: 10.1021/jacs.3c02049] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
The immunotherapy of deep solid tumors in the human body, such as liver cancer, still faces great challenges, especially the inactivation and insufficient infiltration of immune cells in solid tumor microenvironment. Natural killer (NK) cells are gaining ever-increasing attention owing to their unique features and are expected to play an important role in the liver cancer immunotherapy. However, NK cells are severely insufficient and inactivated in solid liver tumor due to the highly immunosuppressive intratumor microenvironment, resulting in poor clinical therapeutic efficacy. Herein, we propose a mild magnetocaloric regulation approach using a magnetogenetic nanoplatform MNPs@PEI-FA/pDNA (MPFD), which is synthesized by loading a heat-inducible plasmid DNA (HSP70-IL-2-EGFP) on polyethyleneimine (PEI)- and folic acid (FA)-modified ZnCoFe2O4@ZnMnFe2O4 magnetic nanoparticles (MNPs) to promote the proliferation and activation of tumor-infiltrating NK cells under magnetic manipulation without the limitation of penetration depth for orthotopic liver cancer immunotherapy. The magnetothermally responsive MPFD serves as a magnetism-heat nanotransducer to induce the gene transcription of IL-2 cytokine in orthotopic liver tumor for NK cell proliferation and activation. Both in vitro and in vivo results demonstrate that the remote mild magnetocaloric regulation (∼40 °C) by MPFD initiates the HSP70 promoter to trigger the overexpression of IL-2 cytokine for subsequent secretion, leading to in situ expansion and activation of tumor-infiltrating NK cells through the IL-2/IL-2 receptor (IL-2R) pathways and the resulting prominent tumor inhibition. This work not only evidences the great potential of magnetogenetic nanoplatform but also reveals the underlying proliferation and activation mechanism of NK cells in liver cancer treatment by magnetogenetic nanoplatform.
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Affiliation(s)
- Han Jiang
- Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Hao Fu
- Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, China
| | - Tao Min
- Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ping Hu
- Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, China
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai 200092, China
| | - Jianlin Shi
- Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai 200092, China
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18
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Sun Z, Wang T, Wang J, Xu J, Shen T, Zhang T, Zhang B, Gao S, Zhao C, Yang M, Sheng F, Yu J, Hou Y. Self-Propelled Janus Nanocatalytic Robots Guided by Magnetic Resonance Imaging for Enhanced Tumor Penetration and Therapy. J Am Chem Soc 2023; 145:11019-11032. [PMID: 37190936 DOI: 10.1021/jacs.2c12219] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Biomedical micro/nanorobots as active delivery systems with the features of self-propulsion and controllable navigation have made tremendous progress in disease therapy and diagnosis, detection, and biodetoxification. However, existing micro/nanorobots are still suffering from complex drug loading, physiological drug stability, and uncontrollable drug release. To solve these problems, micro/nanorobots and nanocatalytic medicine as two independent research fields were integrated in this study to achieve self-propulsion-induced deeper tumor penetration and catalytic reaction-initiated tumor therapy in vivo. We presented self-propelled Janus nanocatalytic robots (JNCRs) guided by magnetic resonance imaging (MRI) for in vivo enhanced tumor therapy. These JNCRs exhibited active movement in H2O2 solution, and their migration in the tumor tissue could be tracked by non-invasive MRI in real time. Both increased temperature and reactive oxygen species production were induced by near-infrared light irradiation and iron-mediated Fenton reaction, showing great potential for tumor photothermal and chemodynamic therapy. In comparison with passive nanoparticles, these self-propelled JNCRs enabled deeper tumor penetration and enhanced tumor therapy after intratumoral injection. Importantly, these robots with biocompatible components and byproducts exhibited biosecurity in the mouse model. It is expected that our work could promote the combination of micro/nanorobots and nanocatalytic medicine, resulting in improved tumor therapy and potential clinical transformations.
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Affiliation(s)
- Zhaoli Sun
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
- Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, School of Life Sciences, Peking University, Beijing 100871, China
| | - Tao Wang
- Electron Microscopy Laboratory, School of Physics, Peking University, Beijing 100871, China
| | - Jingjing Wang
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Junjie Xu
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Tong Shen
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
- Center for Nanoscale Science and Technology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
| | - Teng Zhang
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Biao Zhang
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Shen Gao
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Chenyang Zhao
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Meng Yang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Fugeng Sheng
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jing Yu
- College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou 310014, China
| | - Yanglong Hou
- Beijing Key Laboratory for Magnetoelectric Materials and Devices (BKL-MMD), School of Materials Science and Engineering, Peking University, Beijing 100871, China
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19
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Wu H, Bu T, Cao Y, Wang Y, Xi J, Li M, Li R, Jia P, Wang L. Double-Enzyme Active Vanadium Nanospheres-Mediated Ratiometric Multicolor Immunosensors for Sensitive Detection of the T-2 Toxin. Anal Chem 2023; 95:5275-5284. [PMID: 36898021 DOI: 10.1021/acs.analchem.2c05197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
Abstract
Owing to its high throughput, simplicity, and rapidity, enzyme-linked immunosorbent assay (ELISA) has attracted much attention in the field of immunoassays. However, the traditional ELISA usually affords a single signal readout and the labeling ability of the enzyme used is poor, resulting in low accuracy and a limited detection range. Herein, a vanadium nanospheres (VNSs)-mediated competitive ratio nanozymes-linked immunosorbent assay (VNSs-RNLISA) was created for the sensitive detection of the T-2 toxin (T-2). As the key to the biosensor, the VNSs with superoxide dismutase-like and peroxidase-like dual-enzyme mimetic activities were synthesized by a one-step hydrothermal method, which oxidized 1,1-diphenyl-2-picryl-hydrazyl fading and catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) color development. Therefore, T-2 could not only be qualitatively measured with the naked eye but also be quantitatively evaluated by monitoring the ratio of absorbance at 450 and 517 nm wavelengths. Moreover, the characterization of a VNSs-labeled antibody probe showed strong dual-enzymatic activity, excellent stability, and high affinity with T-2 [the affinity constant (ka) was approximately 1.36 × 108 M-1], which can significantly improve the detection sensitivity. The limit of detection of VNSs-RNLISA was 0.021 ng/mL, which was approximately 27-fold more sensitive than the single signal nanozymes-linked immunosorbent assay (0.561 ng/mL). Besides, the change in the ratio of absorbance (Δ450/Δ517) decreased linearly in a range of 0.22-13.17 ng/mL, outperforming the detection range of a single-mode nano-enzyme-linked immunosorbent assay using TMB by a factor of 1.6 times. Furthermore, the VNSs-RNLISA was successfully used to identify T-2 in maize and oat samples, with recoveries ranging from 84.216 to 125.371%. Overall, this tactic offered a promising platform for the quick detection of T-2 in food and might broaden the application range of the enzyme-linked immunosorbent assay.
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Affiliation(s)
- Haiyu Wu
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Tong Bu
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,College of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, Henan, China
| | - Yuanyuan Cao
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Ying Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Jia Xi
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Mingyan Li
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Ruixia Li
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Pei Jia
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
| | - Li Wang
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China.,Shenzhen Research Institute, Northwest A&F University, Shenzhen 518000, China
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20
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Zhang J, Tang K, Fang R, Liu J, Liu M, Ma J, Wang H, Ding M, Wang X, Song Y, Yang D. Nanotechnological strategies to increase the oxygen content of the tumor. Front Pharmacol 2023; 14:1140362. [PMID: 36969866 PMCID: PMC10034070 DOI: 10.3389/fphar.2023.1140362] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 03/01/2023] [Indexed: 03/12/2023] Open
Abstract
Hypoxia is a negative prognostic indicator of solid tumors, which not only changes the survival state of tumors and increases their invasiveness but also remarkably reduces the sensitivity of tumors to treatments such as radiotherapy, chemotherapy and photodynamic therapy. Thus, developing therapeutic strategies to alleviate tumor hypoxia has recently been considered an extremely valuable target in oncology. In this review, nanotechnological strategies to elevate oxygen levels in tumor therapy in recent years are summarized, including (I) improving the hypoxic tumor microenvironment, (II) oxygen delivery to hypoxic tumors, and (III) oxygen generation in hypoxic tumors. Finally, the challenges and prospects of these nanotechnological strategies for alleviating tumor hypoxia are presented.
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Affiliation(s)
- Junjie Zhang
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Kaiyuan Tang
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Runqi Fang
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Jiaming Liu
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Ming Liu
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Jiayi Ma
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Hui Wang
- School of Fundamental Sciences, Bengbu Medical College, Bengbu, China
| | - Meng Ding
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
- *Correspondence: Meng Ding, ; Xiaoxiao Wang, ; Dongliang Yang,
| | - Xiaoxiao Wang
- Biochemical Engineering Research Center, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma’anshan, China
- *Correspondence: Meng Ding, ; Xiaoxiao Wang, ; Dongliang Yang,
| | - Yanni Song
- Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, China
| | - Dongliang Yang
- Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, China
- *Correspondence: Meng Ding, ; Xiaoxiao Wang, ; Dongliang Yang,
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21
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Ding X, Zhao Z, Zhang Y, Duan M, Liu C, Xu Y. Activity Regulating Strategies of Nanozymes for Biomedical Applications. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2207142. [PMID: 36651009 DOI: 10.1002/smll.202207142] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/06/2022] [Indexed: 06/17/2023]
Abstract
On accounts of the advantages of inherent high stability, ease of preparation and superior catalytic activities, nanozymes have attracted tremendous potential in diverse biomedical applications as alternatives to natural enzymes. Optimizing the activity of nanozymes is significant for widening and boosting the applications into practical level. As the research of the catalytic activity regulation strategies of nanozymes is boosting, it is essential to timely review, summarize, and analyze the advances in structure-activity relationships for further inspiring ingenious research into this prosperous area. Herein, the activity regulation methods of nanozymes in the recent 5 years are systematically summarized, including size and morphology, doping, vacancy, surface modification, and hybridization, followed by a discussion of the latest biomedical applications consisting of biosensing, antibacterial, and tumor therapy. Finally, the challenges and opportunities in this rapidly developing field is presented for inspiring more and more research into this infant yet promising area.
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Affiliation(s)
- Xiaoteng Ding
- Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China
| | - Zhen Zhao
- Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China
| | - Yanfang Zhang
- Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China
| | - Meilin Duan
- Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China
| | - Chengzhen Liu
- Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China
| | - Yuanhong Xu
- Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, Qingdao, 266071, China
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22
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Chen C, Chen Y, Wang X, Zhang L, Luo Y, Tang Q, Wang Y, Liang X, Ma C. In situ synthesized nanozyme for photoacoustic-imaging-guided photothermal therapy and tumor hypoxia relief. iScience 2023; 26:106066. [PMID: 36818293 PMCID: PMC9929682 DOI: 10.1016/j.isci.2023.106066] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 11/27/2022] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
Nanozymes have attracted extensive research interest due to their ideal enzymatic catalytic performance; however, uncontrollable activities and nonspecific accumulation limit their further clinical application. To overcome these obstacles, we proposed in situ synthesized nanozyme, and realized the concept through an intelligent nanosystem (ISSzyme) based on Prussian blue (PB) precursor. PB nanozyme was synthesized at the tumor sites through the interaction of ISSzyme with glutathione, which was demonstrated by comparing with conventional PB nanozyme. ISSzyme is capable of tumor-specific photoacoustic imaging (PAI) and photothermal therapy (PTT), reducing the false-positive signals of PAI and the treatment side effects of PTT. ISSzyme has catalase-like activities, resulting in tumor hypoxia relief and metastasis inhibition. More importantly, the in situ synthesized PB nanozyme has the favorable property of minimal liver accumulation. Considering the above advantages, ISSzyme is expected to shed light on the design of the next-generation artificial enzymes, with many new biomedical applications.
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Affiliation(s)
- Chaoyi Chen
- Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, China
| | - Yuwen Chen
- Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, China
| | - Xuanhao Wang
- Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, China
| | - Lulu Zhang
- Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China
| | - Yan Luo
- Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, China
| | - Qingshuang Tang
- Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China
| | - Yuan Wang
- Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China
| | - Xiaolong Liang
- Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China,Corresponding author
| | - Cheng Ma
- Department of Electronic Engineering, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, China,Institute for Precision Healthcare, Tsinghua University, Beijing 100084, China,Corresponding author
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23
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Yu Y, Zhao W, Yuan X, Li R. Progress and prospects of nanozymes for enhanced antitumor therapy. Front Chem 2022; 10:1090795. [PMID: 36531332 PMCID: PMC9755492 DOI: 10.3389/fchem.2022.1090795] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 11/21/2022] [Indexed: 09/06/2023] Open
Abstract
Nanozymes are nanomaterials with mimicked enzymatic activity, whose catalytic activity can be designed by changing their physical parameters and chemical composition. With the development of biomedical and material science, artificially created nanozymes have high biocompatibility and can catalyze specific biochemical reactions under biological conditions, thus playing a vital role in regulating physiological activities. Under pathological conditions, natural enzymes are limited in their catalytic capacity by the varying reaction conditions. In contrast, compared to natural enzymes, nanozymes have advantages such as high stability, simplicity of modification, targeting ability, and versatility. As a result, the novel role of nanozymes in medicine, especially in tumor therapy, is gaining increasing attention. In this review, function and application of various nanozymes in the treatment of cancer are summarized. Future exploration paths of nanozymes in cancer therapies based on new insights arising from recent research are outlined.
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Affiliation(s)
| | | | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Li
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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24
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Wang S, Wang Z, Li Z, Xu J, Meng X, Zhao Z, Hou Y. A Catalytic Immune Activator Based on Magnetic Nanoparticles to Reprogram the Immunoecology of Breast Cancer from "Cold" to "Hot" State. Adv Healthc Mater 2022; 11:e2201240. [PMID: 36065620 DOI: 10.1002/adhm.202201240] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/03/2022] [Indexed: 01/28/2023]
Abstract
Triple-negative breast cancer (TNBC) as "cold" tumor is characterized by severe immunosuppression of the tumor microenvironment (TME). To effectively activate the immune response of TNBC, a new kind of therapy strategy called cancer catalytic immunotherapy is proposed based on magnetic nanoparticles (NPs) as immune activators. Utilizing the weak acidity and excessive hydrogen peroxide of TME, these magnetic NPs can release ferrous ions to promote Fenton reaction, leading to abundant ·OH and reactive oxygen species (ROS) for ultimately killing cancer cells. Mechanistically, these magnetic NPs activate the ROS-related signaling pathway to generate more ROS. Meanwhile, these magnetic NPs with unique immunological properties can promote the maturation of dendritic cells and the polarization of macrophages from M2 to M1, resulting in the infiltration of more T cells to reprogram the immunoecology of TNBC from "cold" to "hot" state. Besides directly affecting immune cells, these magnetic NPs can also affect the secretion of some immune-related cytokines by cancer cells, to further indirectly activate the immune response. In conclusion, these catalytic immune activators are designed to achieve the synergistic treatment of chemodynamic therapy-enhanced immunotherapy guided by computed tomography (CT)/near-infrared region-II (NIR-II) dual-mode imaging, providing a new strategy for TNBC treatment.
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Affiliation(s)
- Shuren Wang
- Beijing Key Laboratory of Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Beijing Innovation Centre for Engineering Science and Advanced Technology, Peking University, Beijing, 100871, China
| | - Zhiyi Wang
- Beijing Key Laboratory of Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Beijing Innovation Centre for Engineering Science and Advanced Technology, Peking University, Beijing, 100871, China
| | - Ziyuan Li
- Institute of Medical Technology, Peking University Health Science Center, Peking University, Beijing, 100191, China.,Department of Biomedical Engineering, Peking University, Beijing, 100871, China
| | - Junjie Xu
- Beijing Key Laboratory of Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Beijing Innovation Centre for Engineering Science and Advanced Technology, Peking University, Beijing, 100871, China
| | - Xiangxi Meng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Zijing Zhao
- Beijing Key Laboratory of Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Beijing Innovation Centre for Engineering Science and Advanced Technology, Peking University, Beijing, 100871, China
| | - Yanglong Hou
- Beijing Key Laboratory of Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Beijing Innovation Centre for Engineering Science and Advanced Technology, Peking University, Beijing, 100871, China
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25
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Zúñiga LA, Leßmann T, Uppal K, Bisek N, Hong E, Rasmussen CE, Karlsson JJ, Zettler J, Holten-Andersen L, Bang K, Thakar D, Lee YC, Martinez S, Sabharwal SS, Stark S, Faltinger F, Kracker O, Weisbrod S, Müller R, Voigt T, Bigott K, Tabrizifard M, Breinholt VM, Mirza AM, Rosen DB, Sprogøe K, Punnonen J. Intratumoral delivery of TransCon ™ TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction. Cancer Cell Int 2022; 22:286. [PMID: 36123697 PMCID: PMC9484246 DOI: 10.1186/s12935-022-02708-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/02/2022] [Indexed: 11/11/2022] Open
Abstract
Background Intratumoral (IT) delivery of toll-like receptor (TLR) agonists has shown encouraging anti-tumor benefit in preclinical and early clinical studies. However, IT delivery of TLR agonists may lead to rapid effusion from the tumor microenvironment (TME), potentially limiting the duration of local inflammation and increasing the risk of systemic adverse events. Methods To address these limitations, TransCon™ TLR7/8 Agonist—an investigational sustained-release prodrug of resiquimod that uses a TransCon linker and hydrogel technology to achieve sustained and predictable IT release of resiquimod—was developed. TransCon TLR7/8 Agonist was characterized for resiquimod release in vitro and in vivo, in mice and rats, and was assessed for anti-tumor efficacy and pharmacodynamic activity in mice. Results Following a single IT dose, TransCon TLR7/8 Agonist mediated potent tumor growth inhibition which was associated with sustained resiquimod release over several weeks with minimal induction of systemic cytokines. TransCon TLR7/8 Agonist monotherapy promoted activation of antigen-presenting cells in the TME and tumor-draining lymph nodes, with evidence of activation and expansion of CD8+ T cells in the tumor-draining lymph node and TME. Combination of TransCon TLR7/8 Agonist with systemic immunotherapy further promoted anti-tumor activity in TransCon TLR7/8 Agonist-treated tumors. In a bilateral tumor setting, combination of TransCon TLR7/8 Agonist with systemic IL-2 potentiated tumor growth inhibition in both injected and non-injected tumors and conferred protection against tumor rechallenge following complete regressions. Conclusions Our findings show that a single dose of TransCon TLR7/8 Agonist can mediate sustained local release of resiquimod in the TME and promote potent anti-tumor effects as monotherapy and in combination with systemic immunotherapy, supporting TransCon TLR7/8 Agonist as a novel intratumoral TLR agonist for cancer therapy. A clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist, as monotherapy and in combination with pembrolizumab, in cancer patients is currently ongoing (transcendIT-101; NCT04799054). Supplementary Information The online version contains supplementary material available at 10.1186/s12935-022-02708-6.
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Affiliation(s)
| | | | - Karan Uppal
- Ascendis Pharma, Inc., Redwood City, CA, USA
| | | | - Enping Hong
- Ascendis Pharma, Inc., Redwood City, CA, USA
| | | | | | | | | | - Kathy Bang
- Ascendis Pharma, Inc., Redwood City, CA, USA
| | | | - Yu-Chi Lee
- Ascendis Pharma, Inc., Redwood City, CA, USA
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26
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Chen Z, Yue Z, Wang R, Yang K, Li S. Nanomaterials: A powerful tool for tumor immunotherapy. Front Immunol 2022; 13:979469. [PMID: 36072591 PMCID: PMC9441741 DOI: 10.3389/fimmu.2022.979469] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
Cancer represents the leading global driver of death and is recognized as a critical obstacle to increasing life expectancy. In recent years, with the development of precision medicine, significant progress has been made in cancer treatment. Among them, various therapies developed with the help of the immune system have succeeded in clinical treatment, recognizing and killing cancer cells by stimulating or enhancing the body’s intrinsic immune system. However, low response rates and serious adverse effects, among others, have limited the use of immunotherapy. It also poses problems such as drug resistance and hyper-progression. Fortunately, thanks to the rapid development of nanotechnology, engineered multifunctional nanomaterials and biomaterials have brought breakthroughs in cancer immunotherapy. Unlike conventional cancer immunotherapy, nanomaterials can be rationally designed to trigger specific tumor-killing effects. Simultaneously, improved infiltration of immune cells into metastatic lesions enhances the efficiency of antigen submission and induces a sustained immune reaction. Such a strategy directly reverses the immunological condition of the primary tumor, arrests metastasis and inhibits tumor recurrence through postoperative immunotherapy. This paper discusses several types of nanoscale biomaterials for cancer immunotherapy, and they activate the immune system through material-specific advantages to provide novel therapeutic strategies. In summary, this article will review the latest advances in tumor immunotherapy based on self-assembled, mesoporous, cell membrane modified, metallic, and hydrogel nanomaterials to explore diverse tumor therapies.
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Affiliation(s)
- Ziyin Chen
- Clinical Medicine, Harbin Medical University, Harbin, China
| | - Ziqi Yue
- Department of Forensic Medicine, Harbin Medical University, Harbin, China
| | - Ronghua Wang
- Department of Outpatient, Dongying People’s Hospital, Dongying, China
| | - Kaiqi Yang
- Clinical Medicine, Harbin Medical University, Harbin, China
| | - Shenglong Li
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
- *Correspondence: Shenglong Li, ;
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27
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Sivasubramanian M, Lin LJ, Wang YC, Yang CS, Lo LW. Industrialization’s eye view on theranostic nanomedicine. Front Chem 2022; 10:918715. [PMID: 36059870 PMCID: PMC9437266 DOI: 10.3389/fchem.2022.918715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 07/14/2022] [Indexed: 11/13/2022] Open
Abstract
The emergence of nanomedicines (NMs) in the healthcare industry will bring about groundbreaking improvements to the current therapeutic and diagnostic scenario. However, only a few NMs have been developed into clinical applications due to a lack of regulatory experience with them. In this article, we introduce the types of NM that have the potential for clinical translation, including theranostics, multistep NMs, multitherapy NMs, and nanoclusters. We then present the clinical translational challenges associated with NM from the pharmaceutical industry’s perspective, such as NMs’ intrinsic physiochemical properties, safety, scale-up, lack of regulatory experience and standard characterization methods, and cost-effectiveness compared with their traditional counterparts. Overall, NMs face a difficult task to overcome these challenges for their transition from bench to clinical use.
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