坏死性下垂
内吞作用
单线态氧
光敏剂
程序性细胞死亡
赫拉
光动力疗法
细胞生物学
化学
细胞凋亡
细胞毒性
系统间交叉
顺铂
癌症研究
细胞内
生物物理学
氧气
细胞
生物
体外
生物化学
光化学
单重态
有机化学
物理
遗传学
化疗
核物理学
激发态
作者
Xiao Zheng,Minglun Liu,Yanping Wu,Yuncong Chen,Wei He,Zijian Guo
摘要
Side effects and drug resistance are among the major problems of platinum-based anticancer chemotherapies. Photodynamic therapy could show improved tumor targeting ability and better anticancer effect by region-selective light irradiation. Here, we report an aggregation-induced emission (AIE)-based monofunctional Pt(ii) complex (TTC-Pt), which shows enhanced singlet oxygen production by introduction of a Pt atom to elevate the intersystem crossing (ISC) rate. Moreover, TTC-Pt exhibits decent capacity of inhibition on tumor cell growth upon light irradiation, with negligible dark toxicity compared to the commonly used chemodrug cisplatin. Mechanistic study suggests that TTC-Pt enters HeLa cells via the endocytosis pathway and locates mainly in lysosomes, causing FSP1 down-regulation and intracellular lipid peroxidation accumulation under irradiation, finally leading to ferroptosis and necroptosis. The synergistic dual cell death pathways could help to kill apoptosis-resistant tumor cells. Therefore, TTC-Pt could serve as a potent antitumor photosensitizer, which overcomes the drug resistance with minimum side effects.
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