To design a rapid release liposomal system for cancer therapy, a NIR responsive bubble-generating thermosensitive liposome (BTSL) system combined with photothermal agent (Cypate), doxorubicin (DOX), and NHHCO was developed. Cypate/DOX-BTSL exhibited a good aqueous stability, photostability, and photothermal effect. In vitro release suggested that the amounts of DOX released from BTSL were obviously higher than that of (NH)SO liposomes at 42°C. After NIR irradiation, the hyperthermic temperature induced by Cypate led to the decomposition of NHHCO and the generation of a large number of CO bubbles, triggering a rapid release of drugs. Confocal laser scanning microscope and acridine orange staining indicated that Cypate/DOX-BTSL upon irradiation could facilitate to disrupt the lysosomal membranes and realize endolysosomal escape into cytosol, improving the intracellular uptake of DOX clearly. MTT and trypan blue staining implied that the cell damage of Cypate/DOX-BTSL with NIR irradiation was more severe than that in the groups without irradiation. In vivo results indicated that Cypate/DOX-BTSL with irradiation could dramatically increase the accumulation of DOX in tumor, inhibit tumor growth, and reduce systemic side effects of DOX. These data demonstrated that Cypate/DOX-BTSL has the potential to be used as a NIR responsive liposomal system for a rapid release of drugs in thermochemotherapy.
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http://dx.doi.org/10.2147/IJN.S130861 | DOI Listing |
Acc Chem Res
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Department of Chemistry, The University of Texas at Austin, 105 East 24th Street, Austin, Texas 78712, United States.
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Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Bottlebrush polymers (BBPs) have garnered significant attention as advanced drug delivery systems, capable of transporting a diverse range of therapeutic agents, including both chemical drugs and biologics. Despite their effectiveness, the empty BBP vectors post-drug release may pose long-term safety risks due to their difficult systemic clearance. Here, a responsive degradable BBP platform for cancer therapy is developed, featuring a poly(disulfide) backbone grafted with fluorine-terminated zwitterionic side chains.
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Department of Pharmaceutical Sciences, College of Health and Human Sciences, North Dakota State University, Fargo, North Dakota 58105, United States.
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