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

ABSTRACT 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.