Lysosome-targeted Cyclometalated Ir(III) Complexes as Photosensitizer/Photoredox Catalysis for Cancer Therapy

Abstract

A novel lysosome-targeted photosensitizer/photoredox catalysis based on cyclometalated Ir(III) complex IrL has been designed and synthesized, which exhibited excellent phosphorescence properties and the ability to generate single oxygen (1O2) and photocatalytically oxidize 1,4-dihydronicotinamide adenine dinucleotide (NADH) under light irradiation. Most importantly, the aforementioned activities are significantly enhanced due to protonation under acidic conditions, which make them highly attractive in light-activated tumor therapy, especially for acidic lysosomes and tumor microenvironments. The photocytotoxicity of IrL and the mechanism of cell death have been investigated. Additionally, the tumor-killing ability of IrL under light irradiation was evaluated using a 4T1 tumor-bearing mice model. This work provides a strategy for the development of lysosome-targeted photosensitizer/photoredox catalysis to overcome hypoxic tumors.