Synthesis, photophysical and anticancer properties of mitochondria-targeted phosphorescent cyclometalated iridium(III) N-heterocyclic carbene complexes

Yi Li; Kang-Nan Wang; Liang He; Liang-Nian Ji; Zong-Wan Mao

doi:10.1016/j.jinorgbio.2019.110976

Synthesis, photophysical and anticancer properties of mitochondria-targeted phosphorescent cyclometalated iridium(III) N-heterocyclic carbene complexes

J Inorg Biochem. 2020 Apr:205:110976. doi: 10.1016/j.jinorgbio.2019.110976. Epub 2019 Dec 27.

Authors

Yi Li¹, Kang-Nan Wang², Liang He³, Liang-Nian Ji², Zong-Wan Mao⁴

Affiliations

¹ Key Laboratory of Theoretical Organic Chemistry and Function Molecule, Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, PR China.
² MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, PR China.
³ College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China.
⁴ MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, PR China. Electronic address: cesmzw@mail.sysu.edu.cn.

PMID: 31926377
DOI: 10.1016/j.jinorgbio.2019.110976

Abstract

Metal N-Heterocyclic carbene (NHC) complexes are expected to be new opportunities for the development of anticancer metallodrugs. In this work, two near-infrared (NIR) emitting iridium(III)-NHC complexes Ir1 and Ir2 have been explored as mitochondria-targeted anticancer and photodynamic agents. These complexes are more cytotoxic than cisplatin against the cancer cells screened, and display higher cytotoxicity in the presence of 450 nm and 630 nm LED light. Colocalization and quantitative studies indicated that these complexes could specially localize to mitochondria. Mechanism studies show that these complexes increase intracellular reactive oxygen species (ROS) level, reduce mitochondrial membrane potential (MMP) and induce some degree of early apoptosis. Further studies found that Ir1could induce mitophagy at dark and necrocytosis under the irradiation of 630 nm LED light. The in vitro and in vivo photoxicity studies revealed that Ir1 is a promising photodynamic therapy (PDT) agent and could significantly inhibit tumor growth.

Keywords: Anticancer; Iridium(III) complexes; Mitochondria-targeted; N-heterocyclic carbene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Animals
Antineoplastic Agents* / chemical synthesis
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Coordination Complexes* / chemical synthesis
Coordination Complexes* / chemistry
Coordination Complexes* / pharmacology
Humans
Iridium* / chemistry
Iridium* / pharmacology
Methane / analogs & derivatives
Methane / chemical synthesis
Methane / chemistry
Mice
Mice, Nude
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology
Photochemotherapy*
Photosensitizing Agents / chemical synthesis
Photosensitizing Agents / chemistry
Photosensitizing Agents / pharmacology
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Coordination Complexes
Photosensitizing Agents
carbene
Iridium
Methane