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Issue 1, 2017
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Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(III) complexes

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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

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Publication details

The article was received on 01 Jul 2016, accepted on 22 Aug 2016 and first published on 22 Aug 2016


Article type: Edge Article
DOI: 10.1039/C6SC02901A
Citation: Chem. Sci., 2017,8, 631-640
  • Open access: Creative Commons BY-NC license
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    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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