title: Phosphorescent iridium(III)-bis-N-heterocyclic carbene complexes as mitochondria-targeted theranostic and photodynamic anticancer agents.
abstract: Mitochondria-targeted compounds represent a promising approach to target tumors selectively and overcome resistance to current anticancer therapies. In this work, three cyclometalated iridium(III) complexes (1-3) containing bis-N-heterocyclic carbene (NHC) ligands have been explored as theranostic and photodynamic agents targeting mitochondria. These complexes display rich photophysical properties, which greatly facilitates the study of their intracellular fate. All three complexes are more cytotoxic than cisplatin against the cancer cells screened. 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 these complexes exert their anticancer efficacy by initiating a cascade of events related to mitochondrial dysfunction. Additionally, they display up to 3 orders of magnitude higher cytotoxicity upon irradiation at 365 nm, which is so far the highest photocytotoxic responses reported for iridium complexes.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, PR China.
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, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: He
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, PR China.
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, PR China. Electronic address: cesmzw@mail.sysu.edu.cn.
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C030011:carbene; D007495:Iridium; D008697:Methane
keywords: Iridium(III) complexes; Mitochondrion; N-Heterocyclic carbene; Phosphorescent emission; Theranostic