Type I Photoreaction and Photoinduced Ferroptosis by a Ru(II)Complex to Overcome Tumor Hypoxia in Photodynamic Therapy  

作　　者：Fen Qi Hao Yuan Yuncong Chen Xin-Xin Peng Yanping Wu Weijiang He Zijian Guo 

机构地区：[1]State Key Laboratory of Coordination Chemistry,School of Chemistry and Chemical Engineering,Chemistry and Biomedicine Innovation Center(ChemBIC),Nanjing University,Nanjing 210023,Jiangsu [2]Nanchuang(Jiangsu)Institute of Chemistry and Health,Nanjing 210000,Jiangsu

出　　处：《CCS Chemistry》2023年第7期1583-1591,共9页中国化学会会刊（英文）

基　　金：This work was financially supported by the National Natural Science Foundation of China(grant nos.22122701,21731004,91953201,92153303,21977044,and 21907050);the Natural Science Foundation of Jiangsu Province(grant nos.BK20202004 and BK20190282);the Excellent Research Program of Nanjing University(grant no.ZYJH004).

摘　　要：Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathways that resist PDT-induced apoptosis.Therefore,developing photosensitizers(PSs)that show low O_(2)^(-)dependency and can induce nonapoptotic cell death pathways is critically needed.Herein,a series of Ru(II)polypyridine complex-based PSs,RuNMe,RuH,and RuCN,were synthesized,and their applications against hypoxic tumor cells through PDT were investigated.All three complexes showthe ability to generate the superoxide anion radical(·O_(2)^(-)),which is the type I photoreaction and less O_(2)^(-)dependent.RuNMe shows the best PDT performance against MCF-7 cells and three-dimensional multicellular spheroids,due to its higher cellular uptake and more reactive oxygen species generation.More importantly,RuNMe-incubated MCF-7 cells show photoinduced ferroptosis as evidenced by glutathione peroxidase 4 downregulation and lipid peroxide accumulation.This work not only develops a novel ferroptosis-inducing Ru(II)complex with the type I PDT process but also offers an effective strategy to solve tumor hypoxia in PDT.

关 键 词：ferroptosis photodynamic therapy O2-independent type I photoreaction superoxide anion radical(·O_(2)^(-)) 

分 类 号：R730.5[医药卫生—肿瘤]