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

Science China Chemistry 2022年第5期65卷 870-876页

作者： Shan Wang Chao Chen Jianmin Wu Jianyu Zhang Jacky W.Y.Lam Hongyang Wang Lei Chen Ben Zhong Tang Fudan University Shanghai Cancer Center Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Chemistry Hong 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 Biology Fudan UniversityShanghai 200433China The International Cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China National Center for Liver Cancer Shanghai 200441China Shenzhen Institute of Aggregate Science and Technology School of Science and EngineeringThe Chinese University of Hong KongShenzhen 518172China AIE Institute Guangzhou Development DistrictGuangzhou 510530China

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.

关键词： controlling ROS generation high-performance AIE-PS lipid peroxidation ferroptosis

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