Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy.

Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy.

ACS Appl Mater Interfaces. 2017 Nov 15;:

Authors: Wang FX, Chen MH, Lin YN, Zhang H, Tan CP, Ji LN, Mao Z

Abstract
Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can inhibit several cancerous processes including cell migration, invasion, colony formation and angiogenesis effectively. Interestingly, they show much higher singlet oxygen quantum yield in acidic solution than in neutral solution. Upon irradiation at 425 nm with low energy (1.2 J·cm(-2)), they can induce apoptosis through lysosomal damage, evaluation of ROS level and activation of caspase-3/7. The highest phototoxicity index is > 476 with almost no dark cytotoxicity observed for Ir4. Ir4 can also inhibit tumor growth effectively in nude mice in vivo after photodynamic therapy. An in vitro assay against 70 kinases indicates that MELK, PIK3CA and AMPK are the possible molecular targets. The IC50 of Ir4 towards MELK is 1.27 μM. Our study demonstrates that these Ir(III) complexes are promising anticancer agents with dual functions including metastasis inhibition and lysosome-damaged photodynamic therapy.

PMID: 29140069 [PubMed - as supplied by publisher]

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