title: Coumarin-appended phosphorescent cyclometalated iridium(iii) complexes as mitochondria-targeted theranostic anticancer agents.
abstract: Theranostic anticancer agents incorporating anticancer properties with capabilities for real-time treatment assessment are appealing candidates for chemotherapy. The design of mitochondria-targeted cytotoxic drugs represents a promising approach to target tumors selectively and overcome resistance to current anticancer therapies. In this work, three coumarin-appended phosphorescent cyclometalated iridium(iii) complexes 1-3 have been explored as mitochondria-targeted theranostic anticancer agents. These complexes display rich photophysical properties, which facilitate the study of their intracellular fate. All three complexes can specifically target mitochondria and show much higher antiproliferative activities than cisplatin against various cancer cells including cisplatin-resistant cells. 1-3 can penetrate into human cervical carcinoma (HeLa) cells quickly and efficiently, and they can carry out theranostic functions by simultaneously inducing and monitoring the morphological changes in mitochondria. Mechanism studies show that 1-3 exert their anticancer efficacy by initiating a cascade of events related to mitochondrial dysfunction. Genome-wide transcriptional and Connectivity Map analyses reveal that the cytotoxicity of complex 3 is associated with pathways involved in mitochondrial dysfunction and apoptosis.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. cesmzw@mail.sysu.edu.cn tancaip@mail.sysu.edu.cn.
authors.forename: Rui-Rong
authors.initials: RR
authors.lastname: Ye
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. cesmzw@mail.sysu.edu.cn tancaip@mail.sysu.edu.cn.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Tan
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. cesmzw@mail.sysu.edu.cn tancaip@mail.sysu.edu.cn.
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. cesmzw@mail.sysu.edu.cn tancaip@mail.sysu.edu.cn.
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007495:Iridium / Q000737:chemistry / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068936:Theranostic Nanomedicine
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003374:Coumarins; D017382:Reactive Oxygen Species; D007495:Iridium