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 targe...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.展开更多
基金supported by the Czech Science Foundation(grant 21-27514S)supported by the Ministry of Science and Innovation and FEDER funds(project RTI2018-096891-b-I00,and MultiMetDrugs network RED2018-102471-T)+2 种基金Fundación Séneca-Región de Murcia(project 20857/PI/18)the University of Murcia for a grant(R-1034/2016)Fundación Séneca-Región de Murcia for a grant(project 21234/FPI/19).
文摘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.
