Highly Efficient Ir(III)-Coumarin Photo-Redox Catalyst for Synergetic Multi-Mode Cancer Photo-Therapy |
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| Authors: | Zhongxian Fan Jiaen Xie Dr Tumpa Sadhukhan Chao Liang Can Huang Wenqing Li Tingxuan Li Dr Pingyu Zhang Dr Samya Banerjee Dr Krishnan Raghavachari Dr Huaiyi Huang |
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| Institution: | 1. School of Pharmaceutical Science (Shenzhen), Sun Yat-sen University, Guangzhou, 510275 P. R. China;2. College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, 518060 P. R. China;3. Department of Chemistry, Indiana University, Bloomington, Indiana, 47405 USA;4. Department of Chemistry, Indian Institute of Technology (BHU), Varanasi, UP-221005 India |
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| Abstract: | Four photo-catalysts of the general formula Ir(CO6/ppy)2(L)]Cl where CO6=coumarin 6 ( Ir1 – Ir3 ), ppy=2-phenylpyridine ( Ir4 ), L=4′-(3,5-di-tert-butylphenyl)-2,2′ : 6′,2′′-terpyridine ( Ir1 ), 4′-(3,5-bis(trifluoromethyl)phenyl)-2,2′ : 6′,2′′-terpyridine ( Ir2 and Ir4 ), and 4-(2,2′ : 6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline ( Ir3 ) were synthesized and characterized. These photostable photo-catalysts ( Ir1 – Ir3 ) showed strong visible light absorption between 400–550 nm. Upon light irradiation (465 and 525 nm), Ir1 – Ir3 generated singlet oxygen and induced rapidly photo-catalytic oxidation of cellular coenzymes NAD(P)H. Ir1 – Ir3 showed time-dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo-index (PI=793) than the clinically used photosensitizer, 5-aminolevulinicacid (5-ALA, PI>30) against HeLa cancer cells. The observed necro-apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo-induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo-induced catalytic anticancer activity in mouse models. |
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| Keywords: | anticancer iridium complex NADH photo catalysis photodynamic therapy |
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