Photodegradation of carbonic anhydrase by iridium complexes for induction of immunogenic cell death under hypoxia

Abstract

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–Ir3) targeting carbonic anhydrase IX (CAIX) were designed. Ir1–Ir3 exhibit potent antiproliferative activities in colon cancer cells upon irradiation with visible light (425 nm). The most active complex Ir3 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. Ir3 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.