Photo‐Induced Disproportionation‐Mediated Photodynamic Therapy: Simultaneous Oxidation of Tetrahydrobiopterin and Generation of Superoxide Radicals

Abstract We herein present an approach of photo‐induced disproportionation for preparation of Type‐I photodynamic agents. As a proof of concept, BODIPY‐based photosensitizers were rationally designed and prepared. The photo‐induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH 4 ), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O 2 − ⋅). One of our Type‐I photodynamic agents not only self‐assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O 2 ), with a half‐maximal inhibitory concentration (IC 50 ) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors.