Hydroxyl radical from iridium(III)-based photosensitizer triggers PANoptosis and ferroptosis for hypoxia-tolerant photodynamic immunotherapy

= 0.98 μM) and effective phototoxic index (PI = 3.05). Mechanistically, the •OH produced by Ir1 induced PANoptosis by increasing the expression of cleaved Caspase-3, GSDMD-N, and p-MLKL, and activated ferroptosis through the GSH-GPX4-LPO axis. Subsequently, Ir1 induced immunogenic cell death by enhancing the release of damage-associated molecular patterns under hypoxia, leading to a 1.8-fold increase in dendritic cell maturation. In melanoma-bearing mice, Ir1 achieved 89% reduction in tumor volume and transformed the immunosuppressed "cold" tumors to the inflamed "hot" phenotypes. This work establishes that the efficient •OH generation from iridium(III)-based photosensitizer can synergistically trigger PANoptosis and ferroptosis. This constitutes a viable approach for achieving effective PDI in hypoxic and immunosuppressive TME.