Synergistic Copper-Coordination/Glutathione Reduction Drives an In Situ Type II-to-Type I Photodynamic Switch in Iridium-Based Photosensitizer Nanocomposites for Potentiated Cancer Immunotherapy.

The clinical translation of photodynamic therapy (PDT) faces dual challenges of tumor hypoxia and antioxidant defense mechanisms. To address these limitations, herein tumor microenvironment (TME)-adaptive nanoparticles are rationally designed that enable oxygen-independent PDT while reprogramming immunosuppressive TME. An Ir(III) complex (Ir1) is engineered to achieve copper-mediated and glutathione (GSH)-activated switching of photodynamic modes from oxygen-dependent Type II to hypoxia-tolerant Type I PDT via coordination-induced modulation of electron transfer.