AIE-Pt metallacages with water-sensitized type I photodynamics for enhanced cancer therapy

Photodynamic therapy (PDT) offers precise cancer treatment, yet conventional photosensitizers frequently suffer from aggregation-caused quenching (ACQ) and oxygen dependence. Here, we report a platinum (Pt)-modulated supramolecular metallacage, TPE-Pt-Cage, constructed from aggregation-induced emission (AIE) ligands to overcome these limitations. Pt coordination rigidifies the AIE framework at the molecular level, suppressing intramolecular motions and π-π stacking, while the resulting supramolecular assembly adopts an open architecture with accessible cavities that facilitates oxygen and substrate diffusion. These synergistic structural features empower TPE-Pt-Cage to achieve ROS generation efficiencies far exceeding its precursor and leading commercial photosensitizers under light irradiation. Under hypoxia, TPE-Pt-Cage engages a sequential electron-transfer pathway in which water acts as the oxygen source, producing in situ O₂ that is subsequently converted into O₂•^- and •OH. This mechanism is supported by hypoxia-tolerant radical species production and redox potentials sufficient to oxidize H₂O, enabling dominant type I ROS output when external oxygen is scarce. Together with the intrinsic chemotherapeutic activity of Pt, TPE-Pt-Cage achieves synergistic tumor inhibition in vitro and in vivo. This hypoxia-resilient PDT strategy, combined with Pt-mediated chemotherapy, drives potent tumor suppression and defines a generalizable design principle for developing AIE-based metallacages as effective PDT agents in oxygen-deficient solid tumors.