Highly Efficient Ir(III)-Coumarin Photo-Redox Catalyst for Synergetic Multi-Mode Cancer Photo-Therapy

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.

Automated summary

Four photo-catalysts were synthesized and characterized, showing strong visible light absorption and efficient photo-catalytic oxidation of cellular coenzymes. Among them, Ir2 exhibited superior anti-cancer activity against HeLa cells compared to a clinically used photosensitizer, and demonstrated in vivo photo-induced catalytic anticancer activity in mouse models.