A Long‐Term Plasma Membrane‐Anchored Photosensitizer for Pyroptosis‐Induced Anticancer Therapy

ABSTRACT The development of precise and stable membrane‐anchoring photosensitizers is important but challenging for pyroptosis‐mediated antitumor therapy. Here, we report a tumor cell membrane‐anchored BODIPY photosensitizer ( TPMS ) capable of inducing plasma membrane rupture via the pyroptosis pathway. Its modular structure integrates a BODIPY core and phenothiazine unit to boost reactive oxygen species (ROS) generation, a quaternary ammonium salt for membrane anchoring, and a disulfide bridge for covalent immobilization. In aqueous solution, TPMS self‐assembles into nanoaggregates with intense absorption at 658 nm and efficient type‐I ROS production. Notably, TPMS was covalently immobilized on plasma membranes with a prolonged retention time of at least 2 h and effectively induced pyroptosis of cancer cells upon light irradiation. Furthermore, in vivo studies confirmed its potent tumor eradication efficacy with minimal systemic toxicity. This work not only provides a rational molecular strategy for constructing long‐term membrane‐localized photosensitizers but also highlights the potential of pyroptosis‐mediated anticancer treatment.