Hydroxyl Radical Photoredox Catalysis in Hypoxic Cancer Cells

Photocatalysis, the use of light to drive chemical reactions, is a versatile strategy with impact across chemistry, physics, biology, and medicine. A key application is photodynamic therapy for cancer, in which a photosensitizer activated by light generates reactive oxygen species to trigger a therapeutic effect. Despite its clinical application, the use of currently employed photosensitizers for photodynamic therapy is intrinsically limited due to the low oxygen concentrations inside of tumors. Herein, a photosensitizer that operates through a dual photoredox pathway, producing singlet oxygen in oxygen-rich conditions and hydroxyl radicals under low oxygen conditions, is reported. This design enables strong therapeutic activity in severely oxygen-deficient (drug-resistant) cancer cells where conventional photosensitizers fail. We anticipate, this approach will open new avenues towards the treatment of hypoxic as well as drug-resistant tumors and highlight the potential of photoredox catalysis in medicine.