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Han X, Zhang X, Kang L, Feng S, Li Y, Zhao G. Peptide-modified nanoparticles for doxorubicin delivery: Strategies to overcome chemoresistance and perspectives on carbohydrate polymers. Int J Biol Macromol 2025; 299:140143. [PMID: 39855525 DOI: 10.1016/j.ijbiomac.2025.140143] [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: 12/16/2024] [Revised: 01/07/2025] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
Chemotherapy serves as the primary treatment for cancers, facing challenges due to the emergence of drug resistance. Combination therapy has been developed to combat cancer drug resistance, yet it still suffers from lack of specific targeting of cancer cells and poor accumulation at the tumor site. Consequently, targeted administration of chemotherapy medications has been employed in cancer treatment. Doxorubicin (DOX) is one of the most frequently used chemotherapeutics, functioning by inhibiting topoisomerase activity. Enhancing the anti-cancer effects of DOX and overcoming drug resistance can be accomplished via delivery by nanoparticles. This review will focus on the development of peptide-DOX conjugates, the functionalization of nanoparticles with peptides, the co-delivery of DOX and peptides, as well as the theranostic use of peptide-modified nanoparticles in cancer treatment. The peptide-DOX conjugates have been designed to enhance the targeted delivery to cancer cells by interacting with receptors that are overexpressed on tumor surfaces. Moreover, nanoparticles can be modified with peptides to improve their uptake in tumor cells via endocytosis. Nanoparticles have the ability to co-deliver DOX along with therapeutic peptides for enhanced cancer treatment. Finally, nanoparticles modified with peptides can offer theranostic capabilities by facilitating both imaging and the delivery of DOX (chemotherapy).
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Affiliation(s)
- Xu Han
- Department of Traditional Chinese medicine, The First Hospital of China Medical University, Shenyang, China
| | - Xue Zhang
- Department of Gynecology, The First Hospital of China Medical University, Shenyang, China
| | - Longdan Kang
- Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, China
| | - Shuai Feng
- Department of Otolaryngology, The First Hospital of China Medical University, Shenyang, China.
| | - Yinyan Li
- Department of Ultrasonic Diagnosis, The First Hospital of China Medical University, Shenyang, China.
| | - Ge Zhao
- Department of Obstetrics, The First Hospital of China Medical University, Shenyang, China.
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2
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Wu J, Xu Y, Wu D, Zhou W, Wang P, Gong J, Yang J, Xia X. Melanin/melanin-like nanoparticles in tumor photothermal and targeted therapies. Int J Pharm 2025; 672:125354. [PMID: 39952417 DOI: 10.1016/j.ijpharm.2025.125354] [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: 11/28/2024] [Revised: 01/24/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
Melanin is a pigment found in nature that has good photothermal conversion qualities as well as stability, adaptability, and ease of manufacture. In addition to displaying the inherent properties of melanin, melanin/melanin-like nanoparticles (NPs) also have strong dispersion stability, excellent biocompatibility and biodegradability. Melanin/melanin-like NPs have been extensively studied for tumor therapy due to their unique photothermal properties and ability to target tumor cells. They have demonstrated particular promise in photothermal therapy of cancers. Using photothermal conversion materials to create a thermal effect by light irradiation, photothermal therapy (PTT) is a therapeutic approach that kills tumor cells locally. In this paper, we firstly review the preparation methods and physicochemical properties of melanin/melanin-like NPs, and then systematically and in-depth describe the recent advances of melanin/melanin-like NPs, especially synthetic polydopamine (PDA) melanin, in oncology applications, mainly focusing on tumor photothermal and targeted therapies. In addition, we summarize the advantages of melanin/melanin-like NPs in improving the efficacy of photothermal therapy, reducing toxic side effects, and enhancing tumor targeting, and discuss the current challenges and future directions.
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Affiliation(s)
- Jing Wu
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China
| | - Yilin Xu
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China
| | - Donghai Wu
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China
| | - Wei Zhou
- Hunan Provincial Drug Review and Inspection Center, China
| | - Pingjie Wang
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China
| | - Jing Gong
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China
| | - Jing Yang
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
| | - Xinhua Xia
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
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3
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Yılmaz E, Kacaroglu D, Ozden AK, Aydogan N. Gold nanoparticles decorated FOLFIRINOX loaded liposomes for synergistic therapy of pancreatic cancer. Int J Pharm 2025; 669:125067. [PMID: 39672312 DOI: 10.1016/j.ijpharm.2024.125067] [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: 08/21/2024] [Revised: 12/05/2024] [Accepted: 12/07/2024] [Indexed: 12/15/2024]
Abstract
Pancreatic cancer is predicted to be the second highest cause of cancer deaths by 2030, with a mortality rate of 98 % and a 5-year survival rate of only 4-8 %. FOLFIRINOX which consists of four main ingredients has shown superior efficacy in treating patients with pancreatic cancer compared to other agents and combinations. However, toxicities have prevented full-dose use of FOLFIRINOX. In this study, we present the design of a liposome nanosystem that enables the sequential release of a drug combination that is called FOLFIRINOX using lipid-based nanosystem synergistic chemo/photothermal therapy approaches. The co-eccentric liposome allowed us to locate the drug molecules in different locations giving us the flexibility to release them in a selected order. Core liposome (L2) has a melting temperature of 53.63 °C, it was decorated by gold nanoparticle (L2@AuNP) to bring photothermal responsiveness. The outer liposome structure had a lower melting temperature, which facilitated the sequential release process. The efficacy of photothermal therapy for nanosystem was calculated. The results indicate that coating L2@AuNP nanostructure with L1 liposomes improves efficacy by stabilizing gold nanoparticles. FOLFIRINOX components are encapsulated in a concentric liposome structure according to the order of administration into the body. The concentric liposome structure enables the sequential release of multiple drugs due to the varying phase transition temperatures of the liposomes. The cytotoxic effect of these formulations was evaluated on Panc-1 pancreatic cancer cells; the lowest cell viability was obtained in 4 Liposome(L) under 5 min NIR irradiation. Combination therapy has a higher therapeutic efficacy (70.45 %) when compared to chemotherapy and photothermal therapy used separately. The study's results show the potential of combination therapies to improve therapeutic outcomes, providing a promising path for future research and clinical application.
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Affiliation(s)
- Emine Yılmaz
- Department of Bioengineering, Graduate School of Science and Engineering, Hacettepe University, 06800 Beytepe, Ankara, Turkey
| | - Demet Kacaroglu
- Department of Medical Biology, Faculty of Medicine, Lokman Hekim University, Ankara, Turkey
| | - Ayse Kevser Ozden
- Department of Medical Biology, Faculty of Medicine, Lokman Hekim University, Ankara, Turkey
| | - Nihal Aydogan
- Department of Bioengineering, Graduate School of Science and Engineering, Hacettepe University, 06800 Beytepe, Ankara, Turkey; Department of Chemical Engineering, Faculty of Engineering, Hacettepe University, Ankara, 06800, Turkey.
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Mansha S, Sajjad A, Zarbab A, Afzal T, Kanwal Z, Iqbal MJ, Raza MA, Ali S. Development of pH-Responsive, Thermosensitive, Antibacterial, and Anticancer CS/PVA/Graphene Blended Hydrogels for Controlled Drug Delivery. Gels 2024; 10:205. [PMID: 38534622 DOI: 10.3390/gels10030205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 02/29/2024] [Accepted: 03/04/2024] [Indexed: 03/28/2024] Open
Abstract
Drug delivery techniques based on polymers have been investigated for their potential to improve drug solubility, reduce systemic side effects, and controlled and targeted administration at infection site. In this study, we developed a co-polymeric hydrogel composed of graphene sheets (GNS), polyvinyl alcohol (PVA), and chitosan (CS) that is loaded with methotrexate (MTX) for in vitro liver cancer treatment. Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM) was employed to check the structural properties and surface morphology. Moreover, tests were conducted on the cytotoxicity, hemolytic activity, release kinetics, swelling behaviour and degradation of hydrogels. A controlled release of drug from hydrogel in PBS at pH 7.4 was examined using release kinetics. Maximal drug release in six hours was 97.34%. The prepared hydrogels did not encourage the HepG2 growth and were non-hemolytic. The current study highlights the potential of GNS-based hydrogel loaded with MTX as an encouraging therapy for hepatocellular carcinoma. HepG2 cell viability of MTX-loaded CS-PVA-GNS hydrogel was (IC50 5.87 µg/200 mL) in comparison to free MTX (IC50 5.03 µg/200 mL). These outcomes recommend that hydrogels with GNS ensure improved drug delivery in cancer microenvironment while lessening adverse consequences on healthy cells.
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Affiliation(s)
- Saira Mansha
- Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Punjab, Pakistan
| | - Amna Sajjad
- Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Punjab, Pakistan
| | - Aneeqa Zarbab
- Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Punjab, Pakistan
| | - Tahmina Afzal
- Centre of Excellence in Solid State Physics, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Punjab, Pakistan
| | - Zakia Kanwal
- Department of Zoology, Lahore College for Women University, Lahore 44444, Punjab, Pakistan
| | - Muhammad Javaid Iqbal
- Centre of Excellence in Solid State Physics, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Punjab, Pakistan
| | - Mohsin Ali Raza
- Institute of Metallurgy and Materials Engineering, Faculty of Chemical and Materials Engineering, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Punjab, Pakistan
| | - Sharafat Ali
- Department of Built Environment and Energy Technology, Linnæus University, SE-351 95 Växjö, Sweden
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Meng X, Zhang Z, Qian Y, Wang X, Lin Y, Shi X, Lin W, Zhang M, Wang H. Carbon-Encapsulated Magnetite Nanodoughnut as a NIR-II Responsive Nanozyme for Synergistic Chemodynamic-Photothermal Therapy. Adv Healthc Mater 2023; 12:e2301926. [PMID: 37552521 DOI: 10.1002/adhm.202301926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 07/27/2023] [Indexed: 08/09/2023]
Abstract
Magnetite-based nanozymes have attracted great interest for catalytic cancer therapy enabled by catalyzing hydrogen peroxide (H2 O2 ) to produce highly toxic hydroxyl radicals (•OH) to kill tumor cells. However, their therapeutic efficacies remain low due to insufficient •OH. Here, a light-responsive carbon-encapsulated magnetite nanodoughnuts (CEMNDs) with dual-catalytic activities for photothermal-enhanced chemodynamic therapy (CDT) is reported. The CEMNDs can accumulate in tumor and get into tumor cells and effectively act as peroxidase to convert H2 O2 to •OH that causes tumor cell death. The CEMNDs also possess intrinsic glutathione oxidase-like activity that which catalyzes the oxidation of reduced glutathione and produce lipid peroxidase for enhanced catalytic therapy. Furthermore, the CEMNDs can absorb 1064 nm light to elevate local temperature and increase release of Fe ions for photothermal therapy and enhanced CDT respectively. The in vivo experiments in an aggressive and drug-resistant metastatic mouse model of triple negative breast cancer model demonstrate excellent synergistic anti-tumor function and no measurable systemic toxicity of CEMNDs.
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Affiliation(s)
- Xiangfu Meng
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Zonghui Zhang
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, P. R. China
- School of Basic Medicine, Anhui Medical University, Hefei, Anhui, 230032, P. R. China
| | - Yong Qian
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Xingyu Wang
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Yefeng Lin
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Xinyi Shi
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Wenchu Lin
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
- Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, P. R. China
- School of Basic Medicine, Anhui Medical University, Hefei, Anhui, 230032, P. R. China
| | - Miqin Zhang
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA
| | - Hui Wang
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Science, Hefei, Anhui, 230031, P. R. China
- Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
- Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, P. R. China
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Zhang T, Pan Y, Suo M, Lyu M, Lam JWY, Jin Z, Ning S, Tang BZ. Photothermal-Triggered Sulfur Oxide Gas Therapy Augments Type I Photodynamic Therapy for Potentiating Cancer Stem Cell Ablation and Inhibiting Radioresistant Tumor Recurrence. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2304042. [PMID: 37559173 PMCID: PMC10582409 DOI: 10.1002/advs.202304042] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Indexed: 08/11/2023]
Abstract
Despite advances in cancer therapy, the existence of self-renewing cancer stem cells (CSC) can lead to tumor recurrence and radiation resistance, resulting in treatment failure and high mortality in patients. To address this issue, a near-infrared (NIR) laser-induced synergistic therapeutic platform has been developed by incorporating aggregation-induced emission (AIE)-active phototheranostic agents and sulfur dioxide (SO2 ) prodrug into a biocompatible hydrogel, namely TBH, to suppress malignant CSC growth. Outstanding hydroxyl radical (·OH) generation and photothermal effect of the AIE phototheranostic agent actualizes Type I photodynamic therapy (PDT) and photothermal therapy through 660 nm NIR laser irradiation. Meanwhile, a large amount of SO2 is released from the SO2 prodrug in thermo-sensitive TBH gel, which depletes upregulated glutathione in CSC and consequentially promotes ·OH generation for PDT enhancement. Thus, the resulting TBH hydrogel can diminish CSC under 660 nm laser irradiation and finally restrain tumor recurrence after radiotherapy (RT). In comparison, the tumor in the mice that were only treated with RT relapsed rapidly. These findings reveal a double-boosting ·OH generation protocol, and the synergistic combination of AIE-mediated PDT and gas therapy provides a novel strategy for inhibiting CSC growth and cancer recurrence after RT, which presents great potential for clinical treatment.
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Affiliation(s)
- Tianfu Zhang
- School of Biomedical EngineeringGuangzhou Medical UniversityGuangzhou510182China
- Department of Chemistrythe Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstructionand Guangdong‐Hong Kong‐Macro Joint Laboratory of Optoelectronic and Magnetic Functional MaterialsThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong999077China
| | - You Pan
- Guangxi Medical University Cancer HospitalNanning530000China
| | - Meng Suo
- School of Biomedical EngineeringGuangzhou Medical UniversityGuangzhou510182China
| | - Meng Lyu
- Department of Gastrointestinal Surgery & Department of GeriatricsShenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)ShenzhenGuangdong518020China
| | - Jacky Wing Yip Lam
- Department of Chemistrythe Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstructionand Guangdong‐Hong Kong‐Macro Joint Laboratory of Optoelectronic and Magnetic Functional MaterialsThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong999077China
| | - Zhaokui Jin
- School of Biomedical EngineeringGuangzhou Medical UniversityGuangzhou510182China
| | - Shipeng Ning
- Guangxi Medical University Cancer HospitalNanning530000China
| | - Ben Zhong Tang
- Department of Chemistrythe Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstructionand Guangdong‐Hong Kong‐Macro Joint Laboratory of Optoelectronic and Magnetic Functional MaterialsThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong Kong999077China
- School of Science and EngineeringShenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhenGuangdong518172China
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7
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Migliore M, Combellack T, Williams J, Kornaszewska M, Valtzoglou V, Pirtnieks A. Hyperthermic intrathoracic chemotherapy in thoracic surgical oncology: future challenges of an exciting procedure. Future Oncol 2021; 17:3901-3904. [PMID: 34346242 DOI: 10.2217/fon-2021-0317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Affiliation(s)
- Marcello Migliore
- Thoracic Surgery, Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, UK.,Minimally Invasive Surgery and New Technologies, Polyclinic Rodolico Hospital, Catania, and Department of General Surgery & Medical Specialties, University of Catania, Catania, Italy
| | - Tom Combellack
- Thoracic Surgery, Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, UK
| | - Jennifer Williams
- Thoracic Surgery, Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, UK
| | - Malgorzata Kornaszewska
- Thoracic Surgery, Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, UK
| | - Vasileios Valtzoglou
- Thoracic Surgery, Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, UK
| | - Ainis Pirtnieks
- Thoracic Surgery, Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff, UK
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8
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Sritharan S, Sivalingam N. A comprehensive review on time-tested anticancer drug doxorubicin. Life Sci 2021; 278:119527. [PMID: 33887349 DOI: 10.1016/j.lfs.2021.119527] [Citation(s) in RCA: 209] [Impact Index Per Article: 52.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 03/31/2021] [Accepted: 04/12/2021] [Indexed: 12/18/2022]
Abstract
Doxorubicin or Adriamycin, is one of the most widely used chemotherapeutic drug for treating a myriad of cancers. It induces cell death through multiple intracellular targets: reactive oxygen species generation, DNA-adduct formation, topoisomerase II inhibition, histone eviction, Ca2+ and iron hemostasis regulation, and ceramide overproduction. Moreover, doxorubicin-treated dying cells undergo cellular modifications that enable neighboring dendritic cell activation and enhanced presentation of tumor antigen. In addition, doxorubicin also aids in the immune-mediated clearance of tumor cells. However, the development of chemoresistance and cardiotoxicity side effect has undermined its widespread applicability. Several formulations of doxorubicin and co-treatments with inhibitors, miRNAs, natural compounds and other chemotherapeutic drugs have been essential in reducing its dosage-dependent toxicity and combating the development of resistance. Further, more advanced research into the molecular mechanism of chemoresistance development would be vital in improving the overall survivability of clinical patients and in preventing cancer relapse.
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Affiliation(s)
- Sruthi Sritharan
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603 203 Chengalpattu District, Tamil Nadu, India
| | - Nageswaran Sivalingam
- Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603 203 Chengalpattu District, Tamil Nadu, India.
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880 nm NIR-Triggered Organic Small Molecular-Based Nanoparticles for Photothermal Therapy of Tumor. NANOMATERIALS 2021; 11:nano11030773. [PMID: 33803677 PMCID: PMC8003086 DOI: 10.3390/nano11030773] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 02/24/2021] [Accepted: 03/17/2021] [Indexed: 12/21/2022]
Abstract
Photothermal therapy (PTT) has received constant attention as an efficient cancer therapy method due to locally selective treatment, which is not affected by the tumor microenvironment. In this study, a novel 880 nm near-infrared (NIR) laser-triggered photothermal agent (PTA), 3TT-IC-4Cl, was used for PTT of a tumor in deep tissue. Folic acid (FA) conjugated amphiphilic block copolymer (folic acid-polyethylene glycol-poly (β-benzyl-L-aspartate)10, FA-PEG-PBLA10) was employed to encapsulate 3TT-IC-4Cl by nano-precipitation to form stable nanoparticles (TNPs), and TNPs exhibit excellent photothermal stability and photothermal conversion efficiency. Furthermore, the in vitro results showed TNPs display excellent biocompatibility and significant phototoxicity. These results suggest that 880 nm triggered TNPs have great potential as effective PTAs for photothermal therapy of tumors in deep tissue.
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10
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Gupta N, Malviya R. Understanding and advancement in gold nanoparticle targeted photothermal therapy of cancer. Biochim Biophys Acta Rev Cancer 2021; 1875:188532. [PMID: 33667572 DOI: 10.1016/j.bbcan.2021.188532] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 12/12/2022]
Abstract
The present communication summarizes the importance, understanding and advancement in the photothermal therapy of cancer using gold nanoparticles. Photothermal therapy was used earlier as a single line therapy, but using a combination of photothermal therapy with other therapies like immunotherapy, chemotherapy, photodynamic therapy; efficient therapy management can be achieved. As it was discussed in many studies that gold nanoparticles are treated as idyllic photothermal transducers due to their structural dimensions, which enables them to strongly absorb near infrared light. Gold nanoparticles which are mediated for photothermal therapy can warn cancer cells to chemotherapy, regulate genes and immunotherapy by enhancing the cell permeability and intracellular delivery. The necrosis process and apoptosis depend on the power of laser and temperature within the cancerous tissues which are reached during irradiation. Cells death mechanism is also important because the cells which died through the process of necrosis can endorse secondary tumor growth while the cells which died through apoptosis may provoke the immune response to inhibit the development of secondary tumor growth. To decrease the in vivo barriers, gold nanostructures are again modified with targeting ligand and bio-responsive linker. The manuscript summarizes that the use of gold nanoparticles is capable of inhibiting the growth of cancerous cells by using photothermal therapy which has lesser adverse effects compared to other line therapies.
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Affiliation(s)
- Nandan Gupta
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India.
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11
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A hybrid semiconducting organosilica-based O 2 nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy. Nat Commun 2021; 12:523. [PMID: 33483518 PMCID: PMC7822893 DOI: 10.1038/s41467-020-20860-3] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/07/2020] [Indexed: 12/24/2022] Open
Abstract
The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O2 by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O2 nanoeconomizer pHPFON-NO/O2 to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O2 interacts with the acidic tumor microenvironment to release NO for endogenous O2 conservation; second, it releases O2 in response to mild photothermal effect to enable exogenous O2 infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This “reducing expenditure of O2 and broadening sources” strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response. Tumor hypoxia is a major limitation in radiotherapy, and strategies to address this often fail due to high oxygen consumption. Here, the authors report a nanomaterial assembly for the simultaneous reduction in mitochondrial respiration and to supply oxygen to potentiate radiotherapy.
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12
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Zhang Y, Jiang C. Postoperative cancer treatments: In-situ delivery system designed on demand. J Control Release 2021; 330:554-564. [PMID: 33359583 DOI: 10.1016/j.jconrel.2020.12.038] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/17/2020] [Accepted: 12/18/2020] [Indexed: 02/07/2023]
Abstract
The keys to the prevention of tumor recurrence after operation are the elimination of residual tumor cells and the reversal of microenvironments that induce recurrence. In the formulation of a treatment scheme, building an appropriate drug delivery system is essential. An in-situ drug delivery system (ISDDS) is regarded as an effective treatment route for postoperative use that increases drug delivery efficiency and mitigates side-effects. ISDDS technology has been considerably improved through a clearer understanding of the mechanisms of postoperative recurrence and the development of drug delivery materials. This paper describes the initiation and characteristics of postoperative recurrence mechanisms. Based on this information, design principles for ISDDS are proposed, and a variety of practical drug delivery systems that fulfil specific therapeutic needs are presented. Challenges and future opportunities related to the application of in-situ drug carriers for inhibiting cancer recurrence are also discussed.
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Affiliation(s)
- Yiwen Zhang
- Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Chen Jiang
- Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
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Zhu G, Wang K, Qin H, Zhao X, Chen W, Xu L, Cao W, Guo H. Internal cross-linked polymeric nanoparticles with dual sensitivity for combination therapy of muscle-invasive bladder cancer. J Nanobiotechnology 2020; 18:124. [PMID: 32887622 PMCID: PMC7472706 DOI: 10.1186/s12951-020-00686-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/28/2020] [Indexed: 01/03/2023] Open
Abstract
Background Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. Methods The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. Results The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. Conclusion A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.![]()
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Affiliation(s)
- Guanchen Zhu
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China
| | - Kaikai Wang
- School of Pharmacy, Nantong University, Nantong, 226001, China
| | - Haixiang Qin
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China
| | - Xiaozhi Zhao
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China
| | - Wei Chen
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China
| | - Linfeng Xu
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China
| | - Wenmin Cao
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China
| | - Hongqian Guo
- Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China.
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14
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Santos MA, Wu SK, Regenold M, Allen C, Goertz DE, Hynynen K. Novel fractionated ultrashort thermal exposures with MRI-guided focused ultrasound for treating tumors with thermosensitive drugs. SCIENCE ADVANCES 2020; 6:6/36/eaba5684. [PMID: 32917589 PMCID: PMC7467687 DOI: 10.1126/sciadv.aba5684] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 07/20/2020] [Indexed: 05/04/2023]
Abstract
Thermosensitive liposomes represent an important paradigm in oncology, where hyperthermia-mediated release coupled with thermal bioeffects enhance the effectiveness of chemotherapy. Their widespread clinical adoption hinges upon performing controlled targeted hyperthermia, and a leading candidate to achieve this is temperature-based magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS). However, the current approach to hyperthermia involves exposures lasting tens of minutes to hours, which is not possible to achieve in many circumstances because of blood vessel cooling and respiratory motion. Here, we investigate a novel approach to overcome these limitations: to use fractionated ultrashort (~30 s) thermal exposures (~41° to 45°C) to release doxorubicin from a thermosensitive liposome. This is first demonstrated in a dorsal chamber tumor model using two-photon microscopy. Thermal exposures were then conducted with a rabbit tumor model using a custom MRgFUS system incorporating temperature feedback control. Drug release was confirmed, and longitudinal experiments demonstrated profoundly enhanced tumor growth inhibition and survival.
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Affiliation(s)
- Marc A Santos
- Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Sheng-Kai Wu
- Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | | | - Christine Allen
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
| | - David E Goertz
- Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Kullervo Hynynen
- Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
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15
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Hod T, Freedberg KJ, Motwani SS, Chen M, Frendl G, Leaf DE, Gupta S, Mothi SS, Richards WG, Bueno R, Waikar SS. Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2020; 161:1510-1518. [PMID: 32631662 DOI: 10.1016/j.jtcvs.2020.05.033] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 05/06/2020] [Accepted: 05/11/2020] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin has been used successfully to treat malignant pleural mesothelioma, a highly aggressive malignancy that is rapidly fatal in most cases. We hypothesized that the combination of ischemic injury with nephrotoxic injury from cisplatin would result in high rates of acute kidney injury. METHODS We conducted an observational study in 503 patients to study the risks and outcomes of acute kidney injury after surgical resection of malignant pleural mesothelioma. Eligible subjects underwent extrapleural pneumonectomy or pleurectomy/decortication with or without hyperthermic intraoperative chemotherapy. Acute kidney injury was defined as an increase in creatinine of 26.5 μmol/L or greater within 48 hours of surgery or a 50% or greater increase over 7 days. RESULTS Acute kidney injury developed in 243 patients (48.3%). Severe acute kidney injury requiring renal replacement therapy developed in 16 patients (3.2%). Major significant predictors for acute kidney injury included male sex (odds ratio, 2.98; P < .001), intraoperative cisplatin administration (odds ratio, 3.12; P < .001), previous cisplatin exposure (odds ratio, 1.96; P = .02), hypertension (odds ratio, 1.57; P = .02), and longer surgical time (odds ratio, 1.15 per hour; P = .02). Compared with patients without acute kidney injury, those with severe acute kidney injury had longer length of stay (26 vs 13 days) and a 2.71-fold increased risk of death in multivariable-adjusted models. CONCLUSIONS Acute kidney injury is common after cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin and is associated with poor long-term outcomes. Strategies to prevent postoperative acute kidney injury are needed to improve multimodal treatment of malignant pleural mesothelioma.
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Affiliation(s)
- Tammy Hod
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Mass
| | | | - Shveta S Motwani
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Mass; Adult Survivorship Program, Dana-Farber Cancer Institute, Boston, Mass
| | - Margaret Chen
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Mass
| | - Gyorgy Frendl
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Mass
| | - David E Leaf
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Mass
| | - Shruti Gupta
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Mass
| | | | - William G Richards
- Department of Surgery, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Mass
| | - Raphael Bueno
- Department of Surgery, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Mass
| | - Sushrut S Waikar
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Mass; Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Mass.
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16
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Ruiz-Pérez L, Rizzello L, Wang J, Li N, Battaglia G, Pei Y. Polypyrrole and polyaniline nanocomposites with high photothermal conversion efficiency. SOFT MATTER 2020; 16:4569-4573. [PMID: 32373877 DOI: 10.1039/d0sm00306a] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
The simple and scalable synthesis of poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC)-coated conducting polymer (CP) nanocomposites is described. These functional nanocomposites exhibit tunable absorption in the near-infrared region with relatively high photothermal efficiencies. More importantly, their potential for bio-imaging and therapeutic treatment is proven by cellular uptake and cytotoxicity studies.
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Affiliation(s)
- Lorena Ruiz-Pérez
- Department of Chemistry, University College London, London, WC1H 0AJ, UK. and The EPSRC/JEOL Centre for Liquid Electron Microscopy, London, WC1H 0AJ, UK
| | - Loris Rizzello
- Department of Chemistry, University College London, London, WC1H 0AJ, UK.
| | - Jinping Wang
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072, P. R. China
| | - Nan Li
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072, P. R. China
| | - Giuseppe Battaglia
- Department of Chemistry, University College London, London, WC1H 0AJ, UK. and The EPSRC/JEOL Centre for Liquid Electron Microscopy, London, WC1H 0AJ, UK and Department of Chemical Engineering, University College London, London, UK
| | - Yiwen Pei
- Department of Chemistry, University College London, London, WC1H 0AJ, UK.
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Chen J, Wen K, Chen H, Jiang S, Wu X, Lv L, Peng A, Zhang S, Huang H. Achieving High-Performance Photothermal and Photodynamic Effects upon Combining D-A Structure and Nonplanar Conformation. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2020; 16:e2000909. [PMID: 32249500 DOI: 10.1002/smll.202000909] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/07/2020] [Accepted: 03/07/2020] [Indexed: 06/11/2023]
Abstract
Various organic nanoagents have been developed for photothermal therapy (PTT) and photodynamic therapy (PDT) under near-infrared (NIR) irradiation. Among them, small molecule-based nanoagents are very attractive due to their advantages of well-defined chemical structures, high purity, good reproducibility, and easy processability. However, only a few small molecule-based nanoagents have been developed for PDT under NIR irradiation. Moreover, the mechanism of PDT under NIR is still elusive. Herein, a semiconducting small molecule (BTA) with donor-acceptor-donor structure and twisted conformation is developed for PDT/PTT under NIR irradiation. A large π-conjugated electron-deficient unit is used as the core to couple with two electron-donating units, ensuring the strong absorption under 808 nm. Moreover, the donor-acceptor structures and twisted conformation can reduce the energy gap between the singlet and triplet states (∆EST ) to afford effective intersystem crossing, beneficial for reactive oxygen species generation. The mechanism is probed by experimental and theoretical evidence. Moreover, the BTA nanoparticles exhibit excellent biocompatibility and PTT/PDT in vitro performance under NIR irradiation. This provides a strategy for designing highly efficient PDT/PTT molecular materials.
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Affiliation(s)
- Jingya Chen
- Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, 30 South Puzhu Road, Nanjing, Jiangsu, 211816, P. R. China
| | - Kaikai Wen
- College of Materials Science and Opto-Electronic Technology, Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Hao Chen
- College of Materials Science and Opto-Electronic Technology, Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Sai Jiang
- Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, 30 South Puzhu Road, Nanjing, Jiangsu, 211816, P. R. China
| | - Xiaoxi Wu
- College of Materials Science and Opto-Electronic Technology, Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Lei Lv
- College of Materials Science and Opto-Electronic Technology, Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Aidong Peng
- College of Materials Science and Opto-Electronic Technology, Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Shiming Zhang
- Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, 30 South Puzhu Road, Nanjing, Jiangsu, 211816, P. R. China
| | - Hui Huang
- College of Materials Science and Opto-Electronic Technology, Key Laboratory of Vacuum Physics, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
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18
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Sharma A, Özayral S, Caserto JS, Ten Cate R, Anders NM, Barnett JD, Kandala SK, Henderson E, Stewart J, Liapi E, Rudek MA, Franken NAP, Oei AL, Korangath P, Bunz F, Ivkov R. Increased uptake of doxorubicin by cells undergoing heat stress does not explain its synergistic cytotoxicity with hyperthermia. Int J Hyperthermia 2020; 36:712-720. [PMID: 31345068 PMCID: PMC6934043 DOI: 10.1080/02656736.2019.1631494] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Purpose: A proposed mechanism for the enhanced effectiveness of hyperthermia and doxorubicin (Dox) combinations is increased intracellular Dox concentrations resulting from heat-induced cell stress. The purpose of this study was to determine whether specific varied Dox and heat combinations produce measurable effects greater than the additive combination, and whether these effects can be attributed to heat-induced increases in intracellular Dox concentrations. Methods: HCT116, HT29 and CT26 cells were exposed to Dox and water bath heating independently. A clonogenic survival assay was used to determine cell killing and intracellular Dox concentrations were measured in HCT116 cells with mass spectrometry. Cells were exposed to heating at 42 °C (60 min) and 0.5 μg/ml of Dox at varying intervals. Synergy was determined by curve-fitting and isobologram analysis. Results: All cell lines displayed synergistic effects of combined heating and Dox. A maximum synergistic effect was achieved with simultaneous cell exposure to Dox and heat. For exposures at 42 ° C, the synergistic effect was most pronounced at Dox concentrations <0.5 μg/ml. Increased intracellular concentrations of Dox in HCT116 cells caused by heat-stress did not generate a concomitant thermal enhancement. Conclusions: Simultaneous exposure of HCT116 cells to heating and Dox is more effective than sequential exposure. Heat-induced cell responses are accompanied by increased intracellular Dox concentrations; however, clonogenic survival data do not support this as the cause for synergistic cytotoxicity.
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Affiliation(s)
- Anirudh Sharma
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Sanem Özayral
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Julia S Caserto
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Rosemarie Ten Cate
- b Department of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam , Amsterdam , The Netherlands
| | - Nicole M Anders
- c Department of Oncology, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - James D Barnett
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Sri Kamal Kandala
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA.,d Department of Mechanical Engineering, Johns Hopkins University , Baltimore , MD , USA
| | - Elizabeth Henderson
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Jacqueline Stewart
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Eleni Liapi
- e Department of Radiology and Radiological Sciences, Johns Hopkins Hospital , Baltimore , MD , USA.,f Institute for Nanobiotechnology, Johns Hopkins University , Baltimore , MD , USA
| | - Michelle A Rudek
- c Department of Oncology, Johns Hopkins University School of Medicine , Baltimore , MD , USA.,g Department of Medicine, Johns Hopkins University , Baltimore , MD , USA.,h Division of Clinical Pharmacology, Johns Hopkins University , Baltimore , MD , USA
| | - Nicolaas A P Franken
- b Department of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam , Amsterdam , The Netherlands
| | - Arlene L Oei
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA.,b Department of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam , Amsterdam , The Netherlands
| | - Preethi Korangath
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Fred Bunz
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA.,c Department of Oncology, Johns Hopkins University School of Medicine , Baltimore , MD , USA
| | - Robert Ivkov
- a Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine , Baltimore , MD , USA.,b Department of Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam , Amsterdam , The Netherlands.,d Department of Mechanical Engineering, Johns Hopkins University , Baltimore , MD , USA.,f Institute for Nanobiotechnology, Johns Hopkins University , Baltimore , MD , USA.,i Department of Materials Science and Engineering, Johns Hopkins University , Baltimore , MD , USA
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19
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Dunne M, Regenold M, Allen C. Hyperthermia can alter tumor physiology and improve chemo- and radio-therapy efficacy. Adv Drug Deliv Rev 2020; 163-164:98-124. [PMID: 32681862 DOI: 10.1016/j.addr.2020.07.007] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 07/07/2020] [Accepted: 07/10/2020] [Indexed: 12/20/2022]
Abstract
Hyperthermia has demonstrated clinical success in improving the efficacy of both chemo- and radio-therapy in solid tumors. Pre-clinical and clinical research studies have demonstrated that targeted hyperthermia can increase tumor blood flow and increase the perfused fraction of the tumor in a temperature and time dependent manner. Changes in tumor blood circulation can produce significant physiological changes including enhanced vascular permeability, increased oxygenation, decreased interstitial fluid pressure, and reestablishment of normal physiological pH conditions. These alterations in tumor physiology can positively impact both small molecule and nanomedicine chemotherapy accumulation and distribution within the tumor, as well as the fraction of the tumor susceptible to radiation therapy. Hyperthermia can trigger drug release from thermosensitive formulations and further improve the accumulation, distribution, and efficacy of chemotherapy.
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20
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Emerging hyperthermia applications for pediatric oncology. Adv Drug Deliv Rev 2020; 163-164:157-167. [PMID: 33203538 DOI: 10.1016/j.addr.2020.10.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 10/18/2020] [Accepted: 10/22/2020] [Indexed: 12/16/2022]
Abstract
Local application of hyperthermia has a myriad of effects on the tumor microenvironment as well as the host's immune system. Ablative hyperthermia (typically > 55 °C) has been used both as monotherapy and adjuvant therapy, while mild hyperthermia treatment (39-45 °C) demonstrated efficacy as an adjuvant therapy through enhancement of both chemotherapy and radiation therapy. Clinical integration of hyperthermia has especially great potential in pediatric oncology, where current chemotherapy regimens have reached maximum tolerability and the young age of patients implies significant risks of late effects related to therapy. Furthermore, activation of both local and systemic immune response by hyperthermia suggests that hyperthermia treatments could be used to enhance the anticancer effects of immunotherapy. This review summarizes the state of current applications of hyperthermia in pediatric oncology and discusses the use of hyperthermia in the context of other available treatments and promising pre-clinical research.
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21
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Li G, Hu W, Zhao M, Zhao W, Li F, Liu S, Huang W, Zhao Q. Rational design of near-infrared platinum(ii)-acetylide conjugated polymers for photoacoustic imaging-guided synergistic phototherapy under 808 nm irradiation. J Mater Chem B 2020; 8:7356-7364. [DOI: 10.1039/d0tb01107j] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We have developed a novel near-infrared Pt-acetylide conjugated polymer CP3 with highly efficient photoconversion behaviors for synergistic cancer phototherapy.
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Affiliation(s)
- Guo Li
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Wenbo Hu
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Menglong Zhao
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Weili Zhao
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Feiyang Li
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Shujuan Liu
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Wei Huang
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
| | - Qiang Zhao
- Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors
- Institute of Advanced Materials (IAM)
- Nanjing University of Posts and Telecommunications (NUPT)
- Nanjing 210023
- P. R. China
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Li Z, Chen Y, Yang Y, Yu Y, Zhang Y, Zhu D, Yu X, Ouyang X, Xie Z, Zhao Y, Li L. Recent Advances in Nanomaterials-Based Chemo-Photothermal Combination Therapy for Improving Cancer Treatment. Front Bioeng Biotechnol 2019; 7:293. [PMID: 31696114 PMCID: PMC6817476 DOI: 10.3389/fbioe.2019.00293] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/09/2019] [Indexed: 01/04/2023] Open
Abstract
Conventional chemotherapy for cancer treatment is usually compromised by shortcomings such as insufficient therapeutic outcome and undesired side effects. The past decade has witnessed the rapid development of combination therapy by integrating chemotherapy with hyperthermia for enhanced therapeutic efficacy. Near-infrared (NIR) light-mediated photothermal therapy, which has advantages such as great capacity of heat ablation and minimally invasive manner, has emerged as a powerful approach for cancer treatment. A variety of nanomaterials absorbing NIR light to generate heat have been developed to simultaneously act as carriers for chemotherapeutic drugs, contributing as heat trigger for drug release and/or inducing hyperthermia for synergistic effects. This review aims to summarize the recent development of advanced nanomaterials in chemo-photothermal combination therapy, including metal-, carbon-based nanomaterials and particularly organic nanomaterials. The potential challenges and perspectives for the future development of nanomaterials-based chemo-photothermal therapy were also discussed.
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Affiliation(s)
- Zuhong Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yangjun Chen
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China
| | - Ya Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yan Yu
- Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanhong Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Danhua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaopeng Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoxi Ouyang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhongyang Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yalei Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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23
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Chiang CF, Hsu YH, Liu CC, Liang PC, Miaw SC, Lin WL. Pulsed-wave Ultrasound Hyperthermia Enhanced Nanodrug Delivery Combined with Chloroquine Exerts Effective Antitumor Response and Postpones Recurrence. Sci Rep 2019; 9:12448. [PMID: 31462676 PMCID: PMC6713759 DOI: 10.1038/s41598-019-47345-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 06/28/2019] [Indexed: 12/23/2022] Open
Abstract
Autophagy is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. In this study, we investigated the anti-tumor effect of combining pulsed-wave ultrasound hyperthermia (pUH) enhanced PEGylated liposomal doxorubicin (PLD) delivery with an autophagy inhibitor chloroquine (CQ). BALB/c mice bearing subcutaneous 4T1 tumor received intravenous injection of PLD (10 mg/kg) plus 15-minute on-tumor pUH on Day 5 after tumor implantation and were then fed with CQ (50 mg/kg daily) thereafter. Prolonged suppression of tumor growth was attained with PLD + pUH + CQ treatment, whereas in PLD + pUH group tumors quickly recurred after an initial inhibition. Treatment with CQ monotherapy had no benefit compared to the control group. Immunohistochemical staining and Western blotting showed that autophagy of cancer cells was blocked for the mice receiving CQ. It indicates that PLD + pUH + CQ is a promising strategy to treat cancer for a long-term inhibition.
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Affiliation(s)
- Chi-Feng Chiang
- Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
| | - Yu-Hone Hsu
- Division of Neurosurgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chih-Chun Liu
- Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.,Department of Radiology, Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Shi-Chuen Miaw
- Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Win-Li Lin
- Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan. .,Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
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24
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Dong Q, Yang H, Wan C, Zheng D, Zhou Z, Xie S, Xu L, Du J, Li F. Her2-Functionalized Gold-Nanoshelled Magnetic Hybrid Nanoparticles: a Theranostic Agent for Dual-Modal Imaging and Photothermal Therapy of Breast Cancer. NANOSCALE RESEARCH LETTERS 2019; 14:235. [PMID: 31448377 PMCID: PMC6709082 DOI: 10.1186/s11671-019-3053-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 06/17/2019] [Indexed: 05/08/2023]
Abstract
Targeted theranostic platform that integrates multi-modal imaging and therapeutic function is emerging as a promising strategy for earlier detection and precise treatment of cancer. Herein, we designed targeted gold-nanoshelled poly (lactic-co-glycolic acid) (PLGA) magnetic hybrid nanoparticles carrying anti-human epidermal growth factor receptor 2 (Her2) antibodies (Her2-GPH NPs) for dual-modal ultrasound (US)/magnetic resonance (MR) imaging and photothermal therapy of breast cancer. The agent was fabricated by coating gold nanoshell around PLGA nanoparticles co-loaded with perfluorooctyl bromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs), followed by conjugating with anti-Her2 antibodies. Cell-targeting studies demonstrated receptor-mediated specific binding of the agent to Her2-positive human breast cancer SKBR3 cells, and its binding rate was significantly higher than that of Her2-negative cells (P < 0.001). In vitro, the agent had capabilities for contrast-enhanced US imaging as well as T2-weighted MR imaging with a relatively high relaxivity (r2 = 441.47 mM-1 s-1). Furthermore, the Her2 functionalization of the agent prominently enhanced the US/MR molecular imaging effect of targeted cells by cell-specific binding. Live/dead cell assay and targeted photothermal cytotoxicity experiments confirmed that Her2-GPH NPs could serve as effective photoabsorbers to specifically induce SKBR3 cell death upon near-infrared laser irradiation. In summary, Her2-GPH NPs were demonstrated to be novel targeted theranostic agents with great potential to facilitate early non-invasive diagnosis and adjuvant therapy of breast cancer.
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Affiliation(s)
- Qi Dong
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Hong Yang
- Department of Chemistry, College of Life and Environmental Science, Shanghai Normal University, Shanghai, 200234 China
| | - Caifeng Wan
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Dongdong Zheng
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Zhiguo Zhou
- Department of Chemistry, College of Life and Environmental Science, Shanghai Normal University, Shanghai, 200234 China
| | - Shaowei Xie
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Li Xu
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Jing Du
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
| | - Fenghua Li
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
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Triggering antitumoural drug release and gene expression by magnetic hyperthermia. Adv Drug Deliv Rev 2019; 138:326-343. [PMID: 30339825 DOI: 10.1016/j.addr.2018.10.004] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 09/06/2018] [Accepted: 10/08/2018] [Indexed: 01/08/2023]
Abstract
Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy.
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26
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Xiong Y, Sun F, Zhang Y, Yang Z, Liu P, Zou Y, Yu Y, Tong F, Yi C, Yang S, Xu Z. Polydopamine-mediated bio-inspired synthesis of copper sulfide nanoparticles for T1-weighted magnetic resonance imaging guided photothermal cancer therapy. Colloids Surf B Biointerfaces 2019; 173:607-615. [DOI: 10.1016/j.colsurfb.2018.10.023] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 09/13/2018] [Accepted: 10/09/2018] [Indexed: 11/27/2022]
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27
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Wang Y, Song Y, Zhu G, Zhang D, Liu X. Highly biocompatible BSA-MnO2 nanoparticles as an efficient near-infrared photothermal agent for cancer therapy. CHINESE CHEM LETT 2018. [DOI: 10.1016/j.cclet.2017.12.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Gold-nanobranched-shell based drug vehicles with ultrahigh photothermal efficiency for chemo-photothermal therapy. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2018; 18:303-314. [PMID: 30326275 DOI: 10.1016/j.nano.2018.09.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/11/2018] [Accepted: 09/24/2018] [Indexed: 12/22/2022]
Abstract
Development of combined chemo-photothermal nanoplatform is of great interest for enhancing antitumor efficacy. Herein, a multifunctional drug delivery system was synthesized based on gold-nanobranched coated betulinic acid liposomes (GNBS-BA-Lips) for chemo-photothermal synergistic therapy. In this system, GNBS-BA-Lips exhibited broad near-infrared (NIR) absorption, preferable photothermal response and good photostability under NIR irradiation. Importantly, the gold-nanobranched nanostructure possessed high photothermal conversion efficiency (η = 55.7%), and the temperature change (ΔT) reached 43.2 °C after laser irradiation for 5 min. Upon NIR irradiation, the nanocarriers apparently endowed higher cell uptake, resulting in an enhanced intracellular drug accumulation. Furthermore, the tumor growth inhibition ratio achieved from chemo-photothermal therapy of GNBS-BA-Lips was 86.9 ± 1.1%, which was higher than that of the chemotherapy or photothermal therapy alone, showing an outstanding synergistic anticancer effect. Our data suggested that the nanoplatform should be considered as a critical platform in the development of cancer multi-mode therapies.
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Jiang W, Zhang H, Wu J, Zhai G, Li Z, Luan Y, Garg S. CuS@MOF-Based Well-Designed Quercetin Delivery System for Chemo-Photothermal Therapy. ACS APPLIED MATERIALS & INTERFACES 2018; 10:34513-34523. [PMID: 30215253 DOI: 10.1021/acsami.8b13487] [Citation(s) in RCA: 111] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability, low water solubility, and chemical instability in the neutral and alkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the codelivery of quercetin as an anticancer agent and CuS nanoparticles as a photothermal therapy (PTT) agent for synergistic combination of chemotherapy and PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin and realize active-targeting drug delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from efficient internalization via FA-receptors-mediated endocytosis. The results of in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT agent can work together efficiently under NIR irradiation, thus remarkably improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8-QT multifunctional drug delivery system might be a promising nanoplatform for cancer treatment.
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Affiliation(s)
- Wei Jiang
- School of Pharmaceutical Science, Key Laboratory of Chemical Biology, Ministry of Education , Shandong University , Jinan 250012 , China
| | - Huiyuan Zhang
- School of Pharmaceutical Science, Key Laboratory of Chemical Biology, Ministry of Education , Shandong University , Jinan 250012 , China
| | - Jilian Wu
- School of Pharmaceutical Science, Key Laboratory of Chemical Biology, Ministry of Education , Shandong University , Jinan 250012 , China
| | - Guangxi Zhai
- School of Pharmaceutical Science, Key Laboratory of Chemical Biology, Ministry of Education , Shandong University , Jinan 250012 , China
| | - Zhonghao Li
- Key Lab of Colloid & Interface Chemistry, Ministry of Education , Shandong University , Jinan 250100 , China
| | - Yuxia Luan
- School of Pharmaceutical Science, Key Laboratory of Chemical Biology, Ministry of Education , Shandong University , Jinan 250012 , China
| | - Sanjay Garg
- School of Pharmacy and Medical Sciences , University of South Australia , Adelaide , South Australia 5000 , Australia
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Aiba H, Yamada S, Mizutani J, Yamamoto N, Okamoto H, Hayashi K, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Tsuchiya H, Otsuka T. Efficacy of radio-hyperthermo-chemotherapy as salvage therapy for recurrent or residual malignant soft tissue tumors. Int J Hyperthermia 2018; 35:658-666. [PMID: 30295115 DOI: 10.1080/02656736.2018.1518545] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Recurrence after wide excision or residual tumor after an unplanned excision of a malignant soft tissue sarcoma (STS) is a complex problem, due to a higher recurrence rate and poorer survival rate compared with primary resection. Regional hyperthermia was used, with the expectation that it will enhance the anti-tumor effects of chemotherapy and radiotherapy. This study aimed to assess the efficacy of neoadjuvant concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for salvage of recurrent or residual malignant STS. METHODS We identified 64 patients with recurrent or residual STS treated between 1994 and 2013. After excluding those with low-grade malignancy, with recurrent bone tumor in the soft tissues, with truncal STS, and who declined to participate, 23 patients (7 with recurrence and 16 with residual tumor) underwent RHC. The histologic diagnoses were undifferentiated pleomorphic sarcoma (n = 11), synovial sarcoma (n = 3), leiomyosarcoma and myxoid liposarcoma (n = 2 each), and other histologic types. As primary outcomes, the 5-year overall survival (OS), distant metastasis-free survival (D-MFS), and local control (LC) rates were evaluated by Kaplan-Meier analysis. RESULTS The median follow-up period was 112.3 months. The 5-year OS, D-MFS, and LC were 86.4%, 77.4%, and 86.7%, respectively. In the univariate analysis, tumor depth was considered as a negative prognostic factor for OS and D-MFS, and a positive margin was also a negative prognostic factor for OS, D-MFS LC with retained on Cox proportional hazards model in OS, and D-MFS. CONCLUSION RHC is an effective option for salvage treatment of recurrent and residual STS.
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Affiliation(s)
- Hisaki Aiba
- a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.,b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Satoshi Yamada
- a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan
| | - Jun Mizutani
- a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan
| | - Norio Yamamoto
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Hideki Okamoto
- a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan
| | - Katsuhiro Hayashi
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Akihiko Takeuchi
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Shinji Miwa
- a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.,b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Takashi Higuchi
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Kensaku Abe
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Yuta Taniguchi
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Hiroyuki Tsuchiya
- b Department of Orthopaedic Surgery , Graduate School of Medical Science, Kanazawa University , Kanazawa , Japan
| | - Takanobu Otsuka
- a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan
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Wang F, Huang Q, Wang Y, Shi L, Shen Y, Guo S. NIR-light and GSH activated cytosolic p65-shRNA delivery for precise treatment of metastatic cancer. J Control Release 2018; 288:126-135. [DOI: 10.1016/j.jconrel.2018.09.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 08/22/2018] [Accepted: 09/03/2018] [Indexed: 12/14/2022]
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Li B, Xu Q, Li X, Zhang P, Zhao X, Wang Y. Redox-responsive hyaluronic acid nanogels for hyperthermia- assisted chemotherapy to overcome multidrug resistance. Carbohydr Polym 2018; 203:378-385. [PMID: 30318226 DOI: 10.1016/j.carbpol.2018.09.076] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 09/14/2018] [Accepted: 09/27/2018] [Indexed: 12/16/2022]
Abstract
Although chemotherapy has been widely used in the treatment of many kinds of cancer, drug resistance and side effects are the main obstacles in the cancer chemotherapy that result in an inferior therapeutic outcome. For the design of drug delivery system, extracellular stability and intracellular effective release are also a pair of contradictions. In this research, gold nanorods (AuNRs) loaded hyaluronic acid (HA) nanogels with reduction sensitivity were prepared for the efficient intracellular delivery of doxorubicin (DOX). The aforementioned HA-CysNG@AuNR nanogels with cystamine (Cys) as crosslinker could remain stable in the physiological condition and release DOX rapidly in the mimic intracellular glutathione (GSH) condition. Meanwhile, the cellular uptake efficiency by the human breast carcinoma (MCF-7) cells was enhanced because of the highly expressed HA receptor (CD44) on the cytomembrane. However, further cell experiments verified that it was difficult to achieve desired results for drug-resistant human breast cancer (MCF-7 ADR) cells due to the reduced drug uptake and enhanced drug efflux. Interestingly, this multidrug resistance of MCF-7 ADR cells could be reversed after treated with near-infrared (NIR) light. This might ascribe to the hyperthermia generated by AuNRs under NIR, which suspended drug efflux process and led to excellent hyperthermia-assisted chemotherapy outcome. Overall, our studies suggested that AuNRs loaded reduction-sensitive HA nanogels were excellent candidates of drug carriers to reverse the drug-resistance and induce severe apoptosis of drug-resistant MCF-7 ADR cells.
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Affiliation(s)
- Bangbang Li
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China
| | - Qinan Xu
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China
| | - Xinfang Li
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China
| | - Peng Zhang
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China
| | - Xiao Zhao
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China
| | - Youxiang Wang
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
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Triggered radiosensitizer delivery using thermosensitive liposomes and hyperthermia improves efficacy of radiotherapy: An in vitro proof of concept study. PLoS One 2018; 13:e0204063. [PMID: 30226898 PMCID: PMC6143263 DOI: 10.1371/journal.pone.0204063] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 08/31/2018] [Indexed: 12/28/2022] Open
Abstract
Introduction To increase the efficacy of chemoradiation and decrease its toxicity in normal tissue, a new concept is proposed, local radiosensitizer delivery, which combines triggered release of a radiosensitizer from thermosensitive liposomes with local hyperthermia and radiotherapy. Here, key aspects of this concept were investigated in vitro I) the effect of hyperthermia on the enhancement of radiotherapy by ThermoDox (thermosensitive liposome containing doxorubicin), II) the concentration dependence of the radiosensitizing effect of doxorubicin and III) the sequence of doxorubicin, hyperthermia and radiotherapy maximizing the radiosensitizing effect. Methods Survival of HT1080 (human fibrosarcoma) cells was measured after exposure to ThermoDox or doxorubicin for 60 minutes, at 37 or 43°C, with or without irradiation. Furthermore, cell survival was measured for cells exposed to different doxorubicin concentrations and radiation doses. Finally, cell survival was measured after applying doxorubicin and/or hyperthermia before or after irradiation. Cell survival was measured by clonogenic assay. In addition, DNA damage was assessed by γH2AX staining. Results Exposure of cells to doxorubicin at 37°C resulted in cell death, but exposure to ThermoDox at 37°C did not. In contrast, ThermoDox and doxorubicin at 43°C resulted in similar cytotoxicity, and in combination with irradiation caused a similar enhancement of cell kill due to radiation. Doxorubicin enhanced the radiation effect in a small, but significant, concentration-dependent manner. Hyperthermia showed the strongest enhancement of radiation effect when applied after irradiation. In contrast, doxorubicin enhanced radiation effect only when applied before irradiation. Concurrent doxorubicin and hyperthermia immediately before or after irradiation showed equal enhancement of radiation effect. Conclusion In vitro, ThermoDox resulted in cytotoxicity and enhancement of irradiation effect only in combination with hyperthermia. Therefore hyperthermia-triggered radiosensitizer release from thermosensitive liposomes may ultimately serve to limit toxicities due to the radiosensitizer in unheated normal tissue and result in enhanced efficacy in the heated tumor.
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van Elk M, van den Dikkenberg JB, Storm G, Hennink WE, Vermonden T, Heger M. Preclinical evaluation of thermosensitive poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-grafted liposomes for cancer thermochemotherapy. Int J Pharm 2018; 550:190-199. [PMID: 30130606 DOI: 10.1016/j.ijpharm.2018.08.027] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 08/14/2018] [Accepted: 08/16/2018] [Indexed: 01/15/2023]
Abstract
Thermosensitive liposomes grafted with cholesterol-conjugated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) (chol-pHPMAlac) have been developed for heat-induced release of doxorubicin (DOX). These liposomes release DOX completely during mild hyperthermia, but their interaction with blood cells and cancer cells has not been studied. Following intravenous administration, liposomes may interact with plasma proteins and various types of cells (e.g., endothelial cells, platelets, and macrophages), which would reduce their disposition in the tumor stroma. Interaction between liposomes and platelets may further cause platelet activation and thrombosis, which could lead to vascular occlusion and thromboembolic complications. The aim was to investigate DOX release kinetics in the presence of serum, stability, in vitro uptake by and toxicity to cancer cells and somatic cells, and platelet activating potential of the chol-pHPMAlac liposomes. DOX release was determined spectrofluorometrically. Liposome stability was determined in buffer and serum by dynamic light scattering and nanoparticle tracking analysis. Association with/uptake by and toxicity of empty liposomes to AML-12, HepG2 (both hepatocyte-derived cancer cells), RAW 264.7 (macrophages), and HUVEC (endothelial) cells was assayed in vitro. Platelet activation was determined by analysis of P-selectin expression and fibrinogen binding. DOPE:EPC liposomes (diameter = 135 nm) grafted with 5% chol-pHPMAlac (cloud point (CP) = 16 °C; Mn = 8.5 kDa) released less than 10% DOX at 37 °C in 30 min, whereas complete release took place at 47 °C or higher within 10 min. The size of these liposomes remained stable in buffer and serum during 24 h at 37 °C. Fluorescently labeled but DOX-lacking chol-pHPMAlac-liposomes exhibited poor association with/uptake by all cells under investigation, were not cytotoxic, and did not activate platelets in both buffered solution and whole blood. In conclusion, thermosensitive chol-pHPMAlac-grafted liposomes rapidly release DOX during mild hyperthermia. The liposomes are stable in a physiological milieu, are not taken up by cells that are encountered in an in vivo setting, and are non-antagonistic towards platelets. Chol-pHPMAlac-grafted liposomes are therefore good candidates for DOX delivery to tumors and temperature-triggered release in tumor stroma.
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Affiliation(s)
- Merel van Elk
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Joep B van den Dikkenberg
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Gert Storm
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Wim E Hennink
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Tina Vermonden
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
| | - Michal Heger
- Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Membrane Biochemistry and Biophysics, Bijvoet Center for Biomolecular Research, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands.
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Yang Z, Cheng R, Zhao C, Sun N, Luo H, Chen Y, Liu Z, Li X, Liu J, Tian Z. Thermo- and pH-dual responsive polymeric micelles with upper critical solution temperature behavior for photoacoustic imaging-guided synergistic chemo-photothermal therapy against subcutaneous and metastatic breast tumors. Theranostics 2018; 8:4097-4115. [PMID: 30128039 PMCID: PMC6096383 DOI: 10.7150/thno.26195] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 06/20/2018] [Indexed: 11/05/2022] Open
Abstract
Chemo-photothermal therapy shows great potential for inhibiting tumor growth. However, achieving maximal chemo-photothermal synergistic efficacy is challenging because of the low efficiency of controllable chemo-drug release in response to external or internal triggers. Thus, a nano-delivery system that could effectively achieve photothermal therapy and dual stimuli-responsive (heat and pH) drug release to inhibit both primary breast tumor growth and metastases is required. Methods: Herein, a thermo- and pH-responsive polymer (mPEG-PAAV) with an upper critical solution temperature (UCST) was synthesized to fabricate a DOX- and IR780-loaded micellar system. After systematic studies of the photothermal performance and controllable drug release of mPEG-PAAV micelles/IR780+DOX under NIR irradiation at different pH values, their chemo-photothermal synergetic therapy efficacies were also estimated both in in vitro and in vivo. Results: Because of the photothermal conversion of mPEG-PAAV micelle/IR780+DOX (~200 nm, 3.82 mV), high local temperature could be induced at the tumor site under NIR laser irradiation. This hyperthermia not only produced an enhanced tumor necrosis, but also broke down the micelles under the decreased pH environment, resulting in rapid DOX release and enhanced intracellular drug accumulation after NIR laser irradiation. In addition, photoacoustic imaging (PAI) of mPEG-PAAV/IR780+DOX micelle was adopted to monitor the morphology and micro-vascular distribution of the tumor tissue, which could also guide the chemo-photothermal therapy. Most importantly, the systemic administration of mPEG-PAAV micelles/IR780+DOX combined with NIR laser irradiation could simultaneously eliminate the 4T1 breast tumor and thoroughly suppress lung metastasis without any obvious adverse effects. Conclusion: Herein, a pH- and thermo-dual responsive UCST micelle system was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and PA imaging guidance for chemo-photothermal synergistic therapy of both primary breast tumors and their metastases.
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Affiliation(s)
- Zhe Yang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Rui Cheng
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Chenyang Zhao
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Na Sun
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Huiyan Luo
- Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou 510060, China
| | - Ya Chen
- Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou 510060, China
| | - Zerong Liu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xian Li
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Jie Liu
- Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou 510006, China
| | - Zhongmin Tian
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
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Lyon PC, Gray MD, Mannaris C, Folkes LK, Stratford M, Campo L, Chung DYF, Scott S, Anderson M, Goldin R, Carlisle R, Wu F, Middleton MR, Gleeson FV, Coussios CC. Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial. Lancet Oncol 2018; 19:1027-1039. [PMID: 30001990 PMCID: PMC6073884 DOI: 10.1016/s1470-2045(18)30332-2] [Citation(s) in RCA: 152] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 04/18/2018] [Accepted: 04/20/2018] [Indexed: 01/22/2023]
Abstract
BACKGROUND Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound. METHODS We did an open-label, single-centre, phase 1 trial in a single UK hospital. Adult patients (aged ≥18 years) with unresectable and non-ablatable primary or secondary liver tumours of any histological subtype were considered for the study. Patients received a single intravenous infusion (50 mg/m2) of lyso-thermosensitive liposomal doxorubicin (LTLD), followed by extracorporeal focused ultrasound exposure of a single target liver tumour. The trial had two parts: in part I, patients had a real-time thermometry device implanted intratumourally, whereas patients in part II proceeded without thermometry and we used a patient-specific model to predict optimal exposure parameters. We assessed tumour biopsies obtained before and after focused ultrasound exposure for doxorubicin concentration and distribution. The primary endpoint was at least a doubling of total intratumoural doxorubicin concentration in at least half of the patients treated, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02181075, and is now closed to recruitment. FINDINGS Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 μg/g (SD 0·93) immediately after drug infusion to 8·56 μg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven (70%) of ten patients, satisfying the primary endpoint. Serious adverse events registered were expected grade 4 transient neutropenia in five patients and prolonged hospital stay due to unexpected grade 1 confusion in one patient. Grade 3-4 adverse events recorded were neutropenia (grade 3 in one patient and grade 4 in five patients), and grade 3 anaemia in one patient. No treatment-related deaths occurred. INTERPRETATION The combined treatment of LTLD and non-invasive focused ultrasound hyperthermia in this study seemed to be clinically feasible, safe, and able to enhance intratumoural drug delivery, providing targeted chemo-ablative response in human liver tumours that were refractory to standard chemotherapy. FUNDING Oxford Biomedical Research Centre, National Institute for Health Research.
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Affiliation(s)
- Paul C Lyon
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Radiology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Institute of Biomedical Engineering, University of Oxford, Oxford, UK
| | - Michael D Gray
- Institute of Biomedical Engineering, University of Oxford, Oxford, UK
| | | | - Lisa K Folkes
- CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK
| | - Michael Stratford
- CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK
| | - Leticia Campo
- CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK
| | - Daniel Y F Chung
- Department of Radiology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Shaun Scott
- Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Mark Anderson
- Department of Radiology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Robert Goldin
- Centre for Pathology, Faculty of Medicine, Imperial College London, London, UK
| | - Robert Carlisle
- Institute of Biomedical Engineering, University of Oxford, Oxford, UK
| | - Feng Wu
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Mark R Middleton
- Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Fergus V Gleeson
- Department of Radiology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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Wu X, Wu Y, Wang Z, Liu L, Sun C, Chen Y, Wang C. A Cascade-Targeting Nanocapsule for Enhanced Photothermal Tumor Therapy with Aid of Autophagy Inhibition. Adv Healthc Mater 2018; 7:e1800121. [PMID: 29582583 DOI: 10.1002/adhm.201800121] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Indexed: 12/19/2022]
Abstract
Autophagy is a homeostatic lysosome-dependent metabolic process to eliminate damaged or dysfunctional cellular organelles, which is closely associated with tumor progression. Indocyanine green (ICG) can convert NIR light energy to localized heat for cancer cell and tissue ablation. However, the effect of autophagy modulation on ICG-mediated photothermal therapy remains unknown. In this study, it is found that primaquine (PQ) suppresses autophagy flux at a late stage through the impeding fusion of the autophagosome with the lysosome to form an autophagolysosome, leading to cell apoptosis or necrosis. This autophagosome-lysosome fusion inhibitory effect and the autophagosome accumulation are more evident in the photothermal therapy combined with autophagy inhibition. Motivated by this notable effect, a cascade-targeting nanocapsule (HCP) is constructed using an organic solvent-free strategy to coencapsulate PQ and ICG. By targeting the cluster designation 44 molecule and sequentially enhancing the cell-penetrating peptide-mediated endocytosis, the codelivery of PQ/ICG by HCP achieves selective recognition and reinforces the internalization by MCF-7 cells to exert a synergistic therapeutic effect on MCF-7 cells both in vitro and in vivo. The HCP system for the photothermal and autophagy inhibition combination therapy represents a novel strategy for the treatment of breast cancer.
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Affiliation(s)
- Xilong Wu
- Center for Functional Biomaterials; School of Materials Science and Engineering; Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education; Sun Yat-sen University; Guangzhou 510275 China
| | - Yundi Wu
- Center for Functional Biomaterials; School of Materials Science and Engineering; Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education; Sun Yat-sen University; Guangzhou 510275 China
| | - Zhiyong Wang
- Center for Functional Biomaterials; School of Materials Science and Engineering; Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education; Sun Yat-sen University; Guangzhou 510275 China
| | - Lixin Liu
- Center for Functional Biomaterials; School of Materials Science and Engineering; Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education; Sun Yat-sen University; Guangzhou 510275 China
| | - Chengxin Sun
- Center for Functional Biomaterials; School of Materials Science and Engineering; Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education; Sun Yat-sen University; Guangzhou 510275 China
| | - Yongming Chen
- Center for Functional Biomaterials; School of Materials Science and Engineering; Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education; Sun Yat-sen University; Guangzhou 510275 China
| | - Chun Wang
- Department of Biomedical Engineering; University of Minnesota; Minneapolis MN 55455 USA
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Adwankar MK, Chitnis MP. Effect of Hyperthermia Alone and in Combination with Anticancer Drugs on the Viability of P388 Leukemic Cells. TUMORI JOURNAL 2018; 70:231-4. [PMID: 6740768 DOI: 10.1177/030089168407000304] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Effect of local tumor hyperthermia (42 °C) at various intervals ranging from 1 to S h and in combination with antineoplastic drugs was investigated on P388 murine lymphocytic leukemic cells by using an in vitro-in vivo bioassay method. It was observed that a 1-h exposure resulted in a one log cell kill. In combination studies with hyperthermia and anticancer drugs, 1-h exposure to hyperthermia along with 10 μg/ml in vitro concentration of adriamycin (NSC 23127), vincristine (NSC 67574), or 5-fluorouracil (NSC 19893) resulted in the synergistic cell killing action against P388 leukemic cells. However, cyclophosphamide (NSC 26271) and cytosine arabinoside (NSC 63878) did not show any enhanced therapeutic effect.
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Aiba H, Yamada S, Mizutani J, Yamamoto N, Okamoto H, Hayashi K, Kimura H, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Araki Y, Tsuchiya H, Otsuka T. Preoperative evaluation of the efficacy of radio-hyperthermo-chemotherapy for soft tissue sarcoma in a case series. PLoS One 2018; 13:e0195289. [PMID: 29659611 PMCID: PMC5901917 DOI: 10.1371/journal.pone.0195289] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 03/15/2018] [Indexed: 11/18/2022] Open
Abstract
Purpose Radio-hyperthermo-chemo (RHC) therapy, which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft tissue tumors has been introduced with the aim of decreasing the possibility of local recurrence after surgery. To avoid unnecessary neoadjuvant therapy and to plan the appropriate surgical treatment, surveillance of RHC therapeutic efficacy during treatment is necessary. In this study, we determined the optimal response criteria to evaluate the efficacy of RHC by comparing preoperative images before and after RHC with pathological evaluation of necrosis in the resected tumor. Patients and methods From 2004 to 2014, 20 patients were enrolled into this study. Needle biopsy revealed 6 cases of myxoid liposarcoma, 6 cases of undifferentiated pleomorphic sarcoma, 4 cases of myxofibrosarcoma, and 4 cases of synovial sarcoma. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST, we calculated the responses to RHC therapy by comparing pre- and post-RHC therapy images. In addition, resected specimens underwent pathological analysis to evaluate response based on tumor necrosis. The correlation between assessment based on preoperative images and resected tumors were evaluated by the Spearman’s rank-order correlation coefficient. Result From the surgical specimens, pathological assessment of necrosis in resected tumor were assessed as less than 50% (2 cases), 50–90% (9 cases), 90–99% (6 cases), and total necrosis (3 cases). Use of the RECIST 1.1 underestimated good responders as stable disease (SD) or progressive disease (PD) in 5 out of 15 cases; on the other hand, use of the modified RECIST did not underestimate the pathological assessment of necrosis. The correlations between responses based on preoperative images and those based on histological assessments were 0.23 (RECIST 1.1) and 0.76 (modified RECIST). Conclusion Because pathological responses can be underestimated using the RECIST 1.1, the modified RECIST, which take into consideration tumor viability, as assessed by contrast MRI, should also be considered when evaluating the efficacy of RHC.
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Affiliation(s)
- Hisaki Aiba
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Satoshi Yamada
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
- * E-mail:
| | - Jun Mizutani
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Norio Yamamoto
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Hideki Okamoto
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Katsuhiro Hayashi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Hiroaki Kimura
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Akihiko Takeuchi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Shinji Miwa
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Takashi Higuchi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Kensaku Abe
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Yuta Taniguchi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Yoshihiro Araki
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Hiroyuki Tsuchiya
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Takanobu Otsuka
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
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Arcangeli G, Cividalli A, Mauro F, Nervi C, Pavin G. Enhanced Effectiveness of Adriamycin and Bleomycin Combined with Local Hyperthermia in Neck Node Metastases from Head and Neck Cancers. TUMORI JOURNAL 2018; 65:481-6. [PMID: 91251 DOI: 10.1177/030089167906500409] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The results of this study concern the comparison of the clinical effects of adriamycin (ADM) or bleomycin (BLM) alone and combined with local hyperthermia on 15 patients with multiple (29) neck node metastases from head and neck cancers. With repeated low fractional daily doses of drug a significant though transient tumor regression was obtained in 2/8 and in 3/6 of the lesions treated with ADM or BLM alone, respectively. When the drugs were combined with 42-43°C hyperthermia, an overall response, either complete or partial, was seen in all the lesions. Complete regression was observed in 38% (3/8) and 43% (3/7) of the lesions treated with ADM or BLM, respectively, combined with heat. At a 4-month follow-up, 33% (2/6) and 40% (2/5) of the same groups of lesions remained still undetectable. These results suggest that the combined treatment of drugs and local hyperthermia can be advantageously employed in clinical practice for treating local tumors, especially recurrences in previously irradiated areas.
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Song Y, Wang J, Liu L, Sun Q, You Q, Cheng Y, Wang Y, Wang S, Tan F, Li N. One-Pot Synthesis of a Bismuth Selenide Hexagon Nanodish Complex for Multimodal Imaging-Guided Combined Antitumor Phototherapy. Mol Pharm 2018; 15:1941-1953. [DOI: 10.1021/acs.molpharmaceut.8b00106] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Yilin Song
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Jinping Wang
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Li Liu
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Qi Sun
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Qing You
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Yu Cheng
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Yidan Wang
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Siyu Wang
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Fengping Tan
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
| | - Nan Li
- Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China
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Aiba H, Yamada S, Mizutani J, Yamamoto N, Okamoto H, Hayashi K, Kimura H, Takeuchi A, Miwa S, Kawai A, Yoshimura K, Tsuchiya H, Otsuka T. Clinical outcomes of radio-hyperthermo-chemotherapy for soft tissue sarcoma compared to a soft tissue sarcoma registry in Japan: a retrospective matched-pair cohort study. Cancer Med 2018; 7:1560-1571. [PMID: 29479833 PMCID: PMC5911583 DOI: 10.1002/cam4.1366] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 01/03/2018] [Indexed: 01/03/2023] Open
Abstract
Regional hyperthermia is considered to enhance the antitumor effects of chemotherapy and radiotherapy. In this study, we confirmed the efficacy of concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for neoadjuvant treatment of malignant soft tissue sarcoma (STS). From 1994 to 2013, we performed RHC in 150 patients. This study was limited to 60 patients using the following exclusion criteria: salvage for recurrence or unplanned excision, trunk location, metastasis at initiation, non-STS, and no definitive surgery. As a control group, we collected data from 11,031 patients in the Bone and Soft Tissue Tumor Registry in Japan (BSTT). We performed multivariate logistic regression analysis, and propensity scores were created for comparisons between groups. The primary outcome of this study was to compare oncologic outcomes (5-year local control rate [LC] and overall survival rate [OS]). In the RHC group, two local recurrences (3.3%) occurred, and no patients underwent amputation. Margins of definitive surgery were not identical between groups [wide margins (60.0% vs. 85.3%), marginal margins (28.3% vs. 10.5%), and intralesional margins (7.4% vs. 4.2%), RHC and BSTT groups, respectively, P < 0.001]. After adjustment, the difference in OS was not significant between groups (HR = 1.26, P = 0.532); however, a statistically significant difference in LC was observed (HR = 4.82, P = 0.037). RHC resulted in a high LC at 5 years compared to the BSTT group, and amputation was averted in the RHC group, despite the wider margins in the BSTT group. This indicates that less invasive surgery might be achieved with effective neoadjuvant therapy.
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Affiliation(s)
- Hisaki Aiba
- Department of Orthopedic SurgeryNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Satoshi Yamada
- Department of Orthopedic SurgeryNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
| | - Jun Mizutani
- Department of Orthopedic SurgeryNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
| | - Norio Yamamoto
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Hideki Okamoto
- Department of Orthopedic SurgeryNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
| | - Katsuhiro Hayashi
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Hiroaki Kimura
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Akihiko Takeuchi
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Shinji Miwa
- Department of Orthopedic SurgeryNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Akira Kawai
- Department of Musculoskeletal OncologyNational Cancer Center HospitalTokyoJapan
| | - Kenichi Yoshimura
- Department of BiostatisticsInnovative Clinical Research CenterKanazawa UniversityKanazawaIshikawaJapan
| | - Hiroyuki Tsuchiya
- Department of Orthopedic SurgeryGraduate School of Medical SciencesKanazawa UniversityKanazawaIshikawaJapan
| | - Takanobu Otsuka
- Department of Orthopedic SurgeryNagoya City University Graduate School of Medical SciencesNagoyaAichiJapan
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Yao M, Ma Y, Liu H, Khan MI, Shen S, Li S, Zhao Y, Liu Y, Zhang G, Li X, Zhong F, Jiang W, Wang Y. Enzyme Degradable Hyperbranched Polyphosphoester Micellar Nanomedicines for NIR Imaging-Guided Chemo-Photothermal Therapy of Drug-Resistant Cancers. Biomacromolecules 2018. [PMID: 29514006 DOI: 10.1021/acs.biomac.7b01793] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Multidrug resistance (MDR) is the major cause for chemotherapy failure, which constitutes a formidable challenge in the field of cancer therapy. The synergistic chemo-photothermal treatment has been reported to be a potential strategy to overcome MDR. In this work, rationally designed enzyme-degradable, hyperbranched polyphosphoester nanomedicines were developed for reversing MDR via the codelivery of doxorubicin and IR-780 (hPPEDOX&IR) as combined chemo-photothermal therapy. The amphiphilic hyperbranched polyphosphoesters with phosphate bond as the branching point were synthesized via a simple but robust one-step polycondensation reaction. The self-assembled hPPEDOX&IR exhibited good serum stability, sustained release, preferable tumor accumulation, and enhanced drug influx of doxorubicin in resistant MCF-7/ADR cells. Moreover, the degradation of hPPEDOX&IR was accelerated in the presence of alkaline phosphatase, which was overexpressed in various cancers, resulting in the fast release of encapsulated doxorubicin. The enzyme-degradable polymer generated synergistic chemo-photothermal cytotoxicity against MCF-7/ADR cells and, thus, the efficient ablation of DOX-resistant tumor without regrowth. This delivery system may open a new avenue for codelivery of chemo- and photothermal therapeutics for MDR tumor therapy.
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Affiliation(s)
- Mengqun Yao
- Department of Oncology , the First Affiliated Hospital of Anhui Medical University , Hefei , Anhui 230022 , People's Republic of China.,Department of Oncology , Fuyang Hospital of Anhui Medical University , Fuyang , Anhui 236000 , People's Republic of China
| | | | | | | | | | | | | | | | | | - Xiaoqiu Li
- Department of Oncology , the First Affiliated Hospital of Anhui Medical University , Hefei , Anhui 230022 , People's Republic of China
| | - Fei Zhong
- Department of Oncology , the First Affiliated Hospital of Anhui Medical University , Hefei , Anhui 230022 , People's Republic of China.,Department of Oncology , Fuyang Hospital of Anhui Medical University , Fuyang , Anhui 236000 , People's Republic of China
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Goel S, Ferreira CA, Chen F, Ellison PA, Siamof CM, Barnhart TE, Cai W. Activatable Hybrid Nanotheranostics for Tetramodal Imaging and Synergistic Photothermal/Photodynamic Therapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2018; 30:10.1002/adma.201704367. [PMID: 29266476 PMCID: PMC5805572 DOI: 10.1002/adma.201704367] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 10/03/2017] [Indexed: 05/20/2023]
Abstract
A multifunctional core-satellite nanoconstruct is designed by assembling copper sulfide (CuS) nanoparticles on the surface of [89 Zr]-labeled hollow mesoporous silica nanoshells filled with porphyrin molecules, for effective cancer imaging and therapy. The hybrid nanotheranostic demonstrates three significant features: (1) simple and robust construction from biocompatible building blocks, demonstrating prolonged blood retention, enhanced tumor accumulation, and minimal long-term systemic toxicity, (2) rationally selected functional moieties that interact together to enable simultaneous tetramodal (positron emission tomography/fluorescence/Cerenkov luminescence/Cerenkov radiation energy transfer) imaging for rapid and accurate delineation of tumors and multimodal image-guided therapy in vivo, and (3) synergistic interaction between CuS-mediated photothermal therapy and porphyrin-mediated photodynamic therapy which results in complete tumor elimination within a day of treatment with no visible recurrence or side effects. Overall, this proof-of-concept study illustrates an efficient, generalized approach to design high-performance core-satellite nanohybrids that can be easily tailored to combine a wide variety of imaging and therapeutic modalities for improved and personalized cancer theranostics in the future.
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Affiliation(s)
- Shreya Goel
- Department of Materials Science and Engineering, University of Wisconsin - Madison, WI, 53705, USA
| | - Carolina A Ferreira
- Department of Biomedical Engineering, University of Wisconsin - Madison, WI, 53705, USA
| | - Feng Chen
- Department of Radiology, University of Wisconsin - Madison, WI, 53705, USA
| | - Paul A Ellison
- Department of Medical Physics, University of Wisconsin - Madison, WI, 53705, USA
| | - Cerise M Siamof
- Department of Radiology, University of Wisconsin - Madison, WI, 53705, USA
| | - Todd E Barnhart
- Department of Medical Physics, University of Wisconsin - Madison, WI, 53705, USA
| | - Weibo Cai
- Department of Materials Science and Engineering, University of Wisconsin - Madison, WI, 53705, USA
- Department of Biomedical Engineering, University of Wisconsin - Madison, WI, 53705, USA
- Department of Radiology, University of Wisconsin - Madison, WI, 53705, USA
- Department of Medical Physics, University of Wisconsin - Madison, WI, 53705, USA
- University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA
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Zhou X, Wang L, Xu Y, Du W, Cai X, Wang F, Ling Y, Chen H, Wang Z, Hu B, Zheng Y. A pH and magnetic dual-response hydrogel for synergistic chemo-magnetic hyperthermia tumor therapy. RSC Adv 2018; 8:9812-9821. [PMID: 35540837 PMCID: PMC9078710 DOI: 10.1039/c8ra00215k] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 03/02/2018] [Indexed: 12/03/2022] Open
Abstract
To overcome the toxicity of chemotherapy, increasing attention has been paid to local drug delivery systems (DDSs). pH-Sensitive hydrogels have emerged as promising DDS materials in the biomedical field due to their remarkable characteristics. However, the pH environment in tumor varies from person to person, which makes the applicability of systems based on pH challenging. In this study, we developed a contractible hydroxypropyl methyl cellulose (HPMC)/Fe3O4 hydrogel with dual-response pH and magnetic properties aiming to overcome the limitations of pH-sensitive hydrogel drug delivery systems and further increase their efficiency in tumor therapy. The HPMC/Fe3O4 hydrogel could act as a drug delivery system that combines pH-sensitive triggering and magnetic dual-response drug release for synergistic chemo-magnetic hyperthermia therapy. The drug delivery profile of the HPMC/Fe3O4/doxorubicin hydrochloride (DOX) hydrogel was determined in vitro and revealed a remarkable pH-sensitive performance. After synergistic chemo-magnetic hyperthermia treatment, mice with 4T1 breast cancer xenografts recovered without any recurrence or metastasis, demonstrating the synergistic effect of chemotherapy and magnetic hyperthermia therapy. Meanwhile, reduced toxicity and superior anticancer effects were achieved due to the combined effect of the pH and magnetic hyperthermia response properties. This study demonstrated the high efficacy and low toxicity of the improved design of HPMC/Fe3O4 for drug delivery, which may provide a promising approach for the application of chemo-magnetic hyperthermia cancer therapy. A pH and magnetic dual-responsive hydrogel highly sensitive to tumor acid microenvironment and efficient responsive magnetic-hyperthermia cancer eradication.![]()
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Chen G, Ma B, Wang Y, Xie R, Li C, Dou K, Gong S. CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging. ACS APPLIED MATERIALS & INTERFACES 2017; 9:41700-41711. [PMID: 29154532 PMCID: PMC5915677 DOI: 10.1021/acsami.7b14083] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Cancer remains a major threat to human health due to low therapeutic efficacies of currently available cancer treatment options. Nanotheranostics, capable of simultaneous therapy and diagnosis/monitoring of diseases, has attracted increasing amounts of attention, particularly for cancer treatment. In this study, CuS-based theranostic micelles capable of simultaneous combination chemotherapy and photothermal therapy (PTT), as well as photoacoustic imaging, were developed for targeted cancer therapy. The micelle was formed by a CuS nanoparticle (NP) functionalized by thermosensitive amphiphilic poly(acrylamide-acrylonitrile)-poly(ethylene glycol) block copolymers. CuS NPs under near-infrared (NIR) irradiation induced a significant temperature elevation, thereby enabling NIR-triggered PTT. Moreover, the hydrophobic core formed by poly(acrylamide-acrylonitrile) segments used for drug encapsulation exhibited an upper critical solution temperature (UCST; ∼38 °C), which underwent a hydrophobic-to-hydrophilic transition once the temperature rose above the UCST induced by NIR-irradiated CuS NPs, thereby triggering a rapid drug release and enabling NIR-controlled chemotherapy. The CuS-based micelles conjugated with GE11 peptides were tested in an epidermal growth factor receptor-overexpressing triple-negative breast cancer model. In both two-dimensional monolayer cell and three-dimensional multicellular tumor spheroid models, GE11-tagged CuS-based micelles under NIR irradiation, enabling the combination chemotherapy and PTT, exhibited the best therapeutic outcome due to a synergistic effect. These CuS-based micelles also displayed a good photoacoustic imaging ability under NIR illumination. Taken together, this multifunctional CuS-based micelle could be a promising nanoplatform for targeted cancer nanotheranostics.
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Affiliation(s)
- Guojun Chen
- Department of Materials Science and Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
- Wisconsin Institute for Discovery and Department of Biomedical Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
| | - Ben Ma
- Wisconsin Institute for Discovery and Department of Biomedical Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
| | - Yuyuan Wang
- Department of Materials Science and Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
- Wisconsin Institute for Discovery and Department of Biomedical Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
| | - Ruosen Xie
- Department of Materials Science and Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
- Wisconsin Institute for Discovery and Department of Biomedical Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
| | - Chun Li
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States
| | - Kefeng Dou
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
| | - Shaoqin Gong
- Department of Materials Science and Engineering, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
- Department of Chemistry, University of Wisconsin—Madison, Madison, Wisconsin 53715, United States
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Fang Z, Wang Y, Li H, Yu S, Liu Z, Fan Z, Chen X, Wu Y, Pan X, Li X, Wang C. Combination Treatment of Citral Potentiates the Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with Pirarubicin for Colorectal Cancer. Mol Pharm 2017; 14:3588-3597. [DOI: 10.1021/acs.molpharmaceut.7b00652] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Zhiyuan Fang
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
- Key
Laboratory of Regenerative Biology, South China Institute for Stem
Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine
and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Yu Wang
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Hao Li
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Shuaishuai Yu
- Department
of Biology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Ziying Liu
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Zhichao Fan
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Xiaomin Chen
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Yuying Wu
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Xuebo Pan
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Xiaokun Li
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Cong Wang
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
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Xu J, Gulzar A, Liu Y, Bi H, Gai S, Liu B, Yang D, He F, Yang P. Integration of IR-808 Sensitized Upconversion Nanostructure and MoS 2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2017; 13. [PMID: 28737290 DOI: 10.1002/smll.201701841] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 06/20/2017] [Indexed: 05/17/2023]
Abstract
Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR-excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR-808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)-functionalized silica layer is developed for PDT agent. The two booster effectors (dye-sensitization and core-shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS2 nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS2 nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.
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Affiliation(s)
- Jiating Xu
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Arif Gulzar
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Yuhui Liu
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Huiting Bi
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Shili Gai
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Bin Liu
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Dan Yang
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Fei He
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Piaoping Yang
- Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
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Yang T, Liu L, Deng Y, Guo Z, Zhang G, Ge Z, Ke H, Chen H. Ultrastable Near-Infrared Conjugated-Polymer Nanoparticles for Dually Photoactive Tumor Inhibition. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2017; 29:1700487. [PMID: 28626897 DOI: 10.1002/adma.201700487] [Citation(s) in RCA: 161] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 04/10/2017] [Indexed: 05/22/2023]
Abstract
It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low-bandgap donor-acceptor (D-A)-type conjugated-polymer nanoparticles (CP-NPs) are developed to afford a highly efficient singlet-to-triplet transition and photothermal conversion for near-infrared (NIR) light-induced photodynamic (PDT)/photothermal (PTT) treatment. CP-NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP-NPs undergo singlet-to-triplet intersystem crossing through charge transfer in the excited D-A system and simultaneous nonradiative decay from the electron-deficient electron acceptor isoindigo derivative under single-wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP-NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light-triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP-NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof-of-concept design of D-A-type conjugated-polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.
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Affiliation(s)
- Tao Yang
- Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
| | - Ling Liu
- Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
| | - Yibin Deng
- Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
| | - Zhengqing Guo
- School of Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China
| | - Guobing Zhang
- Key Lab of Special Display Technology, Ministry of Education, National Engineering Lab of Special Display Technology, State Key Lab of Advanced Display Technology Academy of Opto-Electronic Technology, Hefei University of Technology, Hefei, 230009, China
| | - Zhishen Ge
- CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026, China
| | - Hengte Ke
- Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
| | - Huabing Chen
- Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China
- School of Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China
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50
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Hornung M, Werner JM, Schlitt HJ. Applications of hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer. Expert Rev Anticancer Ther 2017; 17:841-850. [PMID: 28715968 DOI: 10.1080/14737140.2017.1357470] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) plays a pivotal role in the current treatment of peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Since the first demonstration, benefits for patients and especially an increase in survival have been described. In recent years, feasibility, efficacy and safety of HIPEC have been improved and progress has been made in understanding its oncological mechanism. Areas covered: In this article, leading publications have been reviewed including clinical trials to describe the clinical presentation of PC due to CRC and present recent evidence of the CRS/HIPEC procedure. The surgical approach including evaluation of the extent of PC is described and, in addition, the article reports about different HIPEC techniques as well as several protocols. Furthermore, the development and prognostic benefit of the combination of intraperitoneal and intravenous chemotherapy are outlined. Consideration has been given in particular to patient selection and the use of HIPEC if complete cytoreduction is not feasible. Expert commentary: The CRS/HIPEC procedure represents a curative approach to treat patients with PC from CRC. However, surgical skills and the HIPEC technique still require specialized oncological centers.
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Affiliation(s)
- Matthias Hornung
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| | - Jens M Werner
- a Department of Surgery , University of Regensburg , Regensburg , Germany
| | - Hans J Schlitt
- a Department of Surgery , University of Regensburg , Regensburg , Germany
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