期刊
BIOMATERIALS
卷 144, 期 -, 页码 53-59出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.08.018
关键词
Activatable photosensitizer; Mitomycin C; Combination therapy; Glutathione
资金
- Singapore Ministry of Education [R279-000-391-112]
- Singapore NRF Investigatorship [R279-000-444-281]
- National University of Singapore [R279-000-482-133]
- Institute of Materials Research and Engineering of Singapore [IMRE/14-8P1110]
Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy. (C) 2017 Elsevier Ltd. All rights reserved.
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