A mitochondria-targeted AIE photosensitizer for enhancing specificity and efficacy of ferroptosis inducer

作     者：Shan Wang Chao Chen Jianmin Wu Jianyu Zhang Jacky W.Y.Lam Hongyang Wang Lei Chen Ben Zhong Tang Shan Wang;Chao Chen;Jianmin Wu;Jianyu Zhang;Jacky W.Y.Lam;Hongyang Wang;Lei Chen;Ben Zhong Tang

作者机构：Fudan University Shanghai Cancer CenterShanghai Medical CollegeFudan UniversityShanghai 200032China Department of ChemistryHong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionInstitute for Advanced StudyState Key Laboratory of Molecular NanoscienceDivision of Life Scienceand Department of Chemical and Biological EngineeringThe Hong Kong University of Science and TechnologyHong Kong 999077China Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200433China The International Cooperation Laboratory on Signal TransductionEastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China National Center for Liver CancerShanghai 200441China Shenzhen Institute of Aggregate Science and TechnologySchool of Science and EngineeringThe Chinese University of Hong KongShenzhen 518172China AIE InstituteGuangzhou Development DistrictGuangzhou 510530China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2022年第65卷第5期

页      面：870-876页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 0703[理学-化学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81790633,61922047,81830054,81902412,81903184,81988101,91859205,21788102,51620105009) the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-0007-E00065,21XD1404600) the Research Grants Council of Hong Kong(16306620,N_HKUST609/19 and C6014-20W) the Innovation and Technology Commission(ITC-CNERC14SC01,ITCPD/17-9,MHP/047/19 and ITS/301/18FX) the support of Shanghai Key Laboratory of Hepato-biliary Tumor Biology Military Key Laboratory on Signal Transduction supported by the Innovation Program of Shanghai Municipal Education Commission 

主　　题：controlling ROS generation high-performance AIE-PS lipid peroxidation ferroptosis 

摘      要：Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor ***,the specificity and efficacy of ferroptosis inducers remain ***,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light *** administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in ***,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)*** study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.