Lysosome-Targeted Iridium(III)-BODIPY Conjugates with GSH-Activatable Reactive Oxygen Species Generation for Enhanced Photodynamic Immunotherapy of Melanoma

Melanoma represents a major clinical challenge due to its aggressive nature, high metastatic potential, and resistance to conventional therapies. Herein, we developed two near-infrared iridium(III)-BODIPY conjugates (BODIPY-1-Ir and BODIPY-2-Ir) for glutathione (GSH)-activated photodynamic immunotherapy. These conjugates function as lysosome-targeting photosensitizers that deplete intracellular GSH to disrupt redox balance and enhance reactive oxygen species generation with light irradiation. The phototoxicity further induces cascading dendritic cell maturation and tumor-associated macrophage reprogramming, promoting immunogenic cell death. Both in vitro and in vivo studies demonstrated their excellent biocompatibility, strong photodynamic anticancer efficiency, and significant tumor growth inhibition, highlighting their potential as promising candidates for melanoma treatment.