Issue 1, 2017

Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes

Abstract

Cancer cell metabolism is reprogrammed to sustain the high metabolic demands of cell proliferation. Recently, emerging studies have shown that mitochondrial metabolism is a potential target for cancer therapy. Herein, four mitochondria-targeted phosphorescent cyclometalated iridium(III) complexes have been designed and synthesized. Complexes 2 and 4, containing reactive chloromethyl groups for mitochondrial fixation, show much higher cytotoxicity than complexes 1 and 3 without mitochondria-immobilization properties against the cancer cells screened. Further studies show that complexes 2 and 4 induce caspase-dependent apoptosis through mitochondrial damage, cellular ATP depletion, mitochondrial respiration inhibition and reactive oxygen species (ROS) elevation. The phosphorescence of complexes 2 and 4 can be utilized to monitor the perinuclear clustering of mitochondria in real time, which provides a reliable and convenient method for in situ monitoring of the therapeutic effect and gives hints for the investigation of anticancer mechanisms. Genome-wide transcriptional analysis shows that complex 2 exerts its anticancer activity through metabolism repression and multiple cell death signalling pathways. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of phosphorescent iridium complexes.

Graphical abstract: Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes

Supplementary files

Article information

Article type
Edge Article
Submitted
01 Jul 2016
Accepted
22 Aug 2016
First published
22 Aug 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 631-640

Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(III) complexes

J. Cao, C. Tan, M. Chen, N. Wu, D. Yao, X. Liu, L. Ji and Z. Mao, Chem. Sci., 2017, 8, 631 DOI: 10.1039/C6SC02901A

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