BODIPY-Based Photosensitizer with Outstanding Photocytotoxicity for Deep-Tissue Photodynamic Therapy

Tissue penetration and hypoxia present significant challenges for photodynamic therapy (PDT), restricting its clinical utility. We here report a Type-I photosensitizer (OBDP) with outstanding photocytotoxicity to overcome these limitations for deep-tissue PDT. OBDP targets lipid droplets in cancer cells. Upon irradiation, OBDP oxidizes nearby polyunsaturated fatty acids (PUFAs) into hydroperoxides through a photoinduced electron transfer mechanism, ultimately evoking ferroptosis. Under ultralow-power light-irradiation (660 nm, 5 mW cm–2, 3 J cm–2), OBDP effectively kills cancer cells, displaying an impressively low half-maximal inhibitory concentration (IC50) of 55.5–76.3 nM for three cancer cell lines (HeLa, A549, and HepG2 cells) under hypoxic conditions (2% O2). Due to the outstanding photocytotoxicity, OBDP can efficiently ablate tumors in deep-tissue PDT model experiments, achieving a tumor growth inhibition rate of up to 88.1%. This work represents a significant advancement in PDT and offers valuable insights for the development of photosensitizers tailored for deep-tissue solid tumors.