Carbonic anhydrase is an important cancer molecular target and plays important roles in cancer immune functions and maintenance of microenvironments.Herein,three Ir_((III))photosensitizers(Ir1-Ir_(3))targeting carboni...Carbonic anhydrase is an important cancer molecular target and plays important roles in cancer immune functions and maintenance of microenvironments.Herein,three Ir_((III))photosensitizers(Ir1-Ir_(3))targeting carbonic anhydrase IX(CAIX)were designed.Ir1-Ir_(3)exhibit potent antiproliferative activities in colon cancer cells upon irradiation with visible light(425 nm).The most active complex Ir_(3)can photodegrade CAIX under hypoxia,which downregulates the expression of hypoxic inducible factor-1(HIF-1α)and vascular endothelial growth factor(VEGF)to improve cancer immune microenvironments.Ir_(3)can induce pyroptosis of cancer cells through lipid peroxidation,which causes immunogenic cell death(ICD)under hypoxia.In all,we present a new design strategy for small molecules that can improve tumor microenvironments and induce ICD by targeted protein photodegradation,which may bring innovation in the design of novel photoimmunotherapeutic agents.展开更多
基金supported by the National Natural Science Foundation of China(No.22022707,22107124,22177142,22107074 and 21837006)the China Postdoctoral Science Foundation(No.2021M693604 and 2021M692188)the Fundamental Research Funds for the Central Universities。
文摘Carbonic anhydrase is an important cancer molecular target and plays important roles in cancer immune functions and maintenance of microenvironments.Herein,three Ir_((III))photosensitizers(Ir1-Ir_(3))targeting carbonic anhydrase IX(CAIX)were designed.Ir1-Ir_(3)exhibit potent antiproliferative activities in colon cancer cells upon irradiation with visible light(425 nm).The most active complex Ir_(3)can photodegrade CAIX under hypoxia,which downregulates the expression of hypoxic inducible factor-1(HIF-1α)and vascular endothelial growth factor(VEGF)to improve cancer immune microenvironments.Ir_(3)can induce pyroptosis of cancer cells through lipid peroxidation,which causes immunogenic cell death(ICD)under hypoxia.In all,we present a new design strategy for small molecules that can improve tumor microenvironments and induce ICD by targeted protein photodegradation,which may bring innovation in the design of novel photoimmunotherapeutic agents.
