Reprogramming Photosensitization Mechanisms for Hypoxic Tumor Therapy via Organic Photovoltaic-Inspired Heterojunctions.

Conventional Type II photodynamic therapy (PDT) is severely compromised by tumor hypoxia. Drawing inspiration from the charge-separation principles of organic photovoltaics (OPV), we herein show that a molecularly predefined donor-acceptor interface can re-route the excited-state fate of a classical Type II photosensitizer. Electrostatic co-assembly of cationic Y6-2Pr with anionic Rose Bengal (RB) furnishes a stoichiometrically defined 1:2 heterojunction, in which ultrafast intermolecular electron transfer gives rise to an interfacial charge-transfer-to-charge-separated (CT → CS) evolution. This process strongly attenuates triplet-mediated singlet-oxygen sensitization and redirects the photochemistry of RB toward a hypoxia-tolerant Type I pathway dominated by superoxide generation. The photogenerated holes concurrently oxidize NADH, establishing an interfacial photoredox cycle that weakens intracellular reductive defense. By translating a central concept of organic photovoltaic interfaces to photomedicine at the level of a stoichiometrically defined molecular complex, this work provides a route to retrofit classical Type II photosensitizers with Type I photoredox function.