期刊
CHEMBIOCHEM
卷 20, 期 4, 页码 576-586出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201800507
关键词
glutathione; Iridium(III) complexes; photodynamic therapy; photosensitizers; singlet oxygen
资金
- National Natural Science Foundation of China [51473078, 21501098, 21671108]
- National Program for Support of Top-Notch Young Professionals, Scientific and Technological Innovation Teams of Colleges and Universities in Jiangsu Province [TJ215006]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [YX03001]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX17_0751]
It is a huge challenge to avoid irreversible damage to normal tissues during irradiation in photodynamic therapy (PDT) for cancer. An effective strategy is to develop smart photosensitizers, which exhibit amplified generation of reactive oxygen species (ROS) through triggering specific reaction in the tumor microenvironment. In this work, we designed a class of glutathione (GSH)-activatable photosensitizers (Ir1 and Ir4) based on an effective strategy of GSH-induced nucleophilic substitution reaction. The addition of GSH, induced changes in both phosphorescence intensity and lifetime of photosensitizers with high sensitivity. Importantly, the amount of singlet oxygen generated was increased significantly by GSH-induced activation reaction. Hence, the photosensitizers can selectively distinguish cancer cells from normal cells through luminescence and lifetime imaging, and can amplify PDT effects in cancer cells, owing to the evidently higher level of GSH compared to normal cells. This work presents a novel paradigm for GSH-amplified PDT against cancer cells and provides a new avenue for smart-responsive theranostic systems that can avoid nonspecific damage to normal cells.
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