A photoactivated Ir(iii) complex targets cancer stem cells and induces secretion of damage-associated molecular patterns in melanoma cells characteristic of immunogenic cell death

Several anticancer chemotherapies, while eliminating the bulk of tumor cells, often fail, as they do not obliterate a small fraction of malignant cancer stem cells (CSCs). Thus, developing chemotherapeutics capable of targeting and abrogating CSCs, including inducing immunogenic cell death in CSCs, is essential for developing new anticancer drugs. Herein, we report octahedral Ir(iii) complexes based on a benzimidazole backbone containing NH groups. The complexes exhibit low toxicity in the dark against human skin melanoma cells and high phototoxicity with blue light irradiation under both normoxic and hypoxic conditions. Additionally, complex 4 induces secretion of damage-associated molecular patterns characteristic of immunogenic cell death (ICD) in melanoma cells when the cells are irradiated with blue light. The results also suggest that the mechanism of the ICD induced by this complex may involve oxidative damage of intracellular targets by photoinduced ROS generation. This property of 4 may allow targeting the photochemotherapy based on 4 selectively to the tumor.