Journal
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Volume 25, Issue 4, Pages 597-607Publisher
SPRINGER
DOI: 10.1007/s00775-020-01783-2
Keywords
Iridium complex; Mitochondria targeted; Anticancer; Phosphorescent
Funding
- National Natural Science Foundation of China [21601210, 21572282, 21701195, 21601208]
- 973 Program [2015CB856301]
- Ministry of Education of China [IRT_17R111]
- Science and Technology Planning Project of Guangdong Province [2013B051000047, 207999]
- Fundamental Research Funds for the Central Universities
- Natural Science Foundation of Hunan Province [2019JJ50188, 2019JJ50145]
- Scientific Research Fund of Hunan Provincial Education Department [18C0340]
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Cyclometalated iridium(III) complexes represent a promising approach to developing new anticancer metallodrugs. In this work, three phosphorescent cyclometalated iridium(III) complexes Ir1-Ir3 have been explored as mitochondria-targeted anticancer agents. All three complexes display higher antiproliferative activity than cisplatin against the cancer cells screened, and with the IC50 values ranging from 0.23 to 5.6 mu M. Colocalization studies showed that these complexes are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy through initiating a series of events related to mitochondrial dysfunction, including depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS) levels, and induction of apoptosis. Graphic abstract Mitochondria-targted cyclometalated iridium complexes induce apoptosis through depolarized mitochondria, elevation of intracellular ROS and activated caspase.
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