Near‐Infrared Self‐Assembled Hydroxyl Radical Generator Based on Photoinduced Cascade Electron Transfer for Hypoxic Tumor Phototherapy

The hydroxyl radical (•OH) is an extremely potent reactive oxygen species that plays a crucial role in photooxidations within the realm of hypoxic tumor therapy. However, the current methods for •OH photogeneration typically rely on inorganic materials that require UV/vis light excitation. Consequently, photogenerators based on organic molecules, especially those utilizing near-infrared (NIR) light excitation, are rare. In this study, the concept of photoinduced cascade charge transfer (PICET), which utilizes NIR heavy-atom-free photosensitizers (ANOR-Cy5) to generate •OH is introduced. The ANOR-Cy5 photosensitizer, with its flexible hydrophobic structure, enables the formation of nanoparticles in aqueous solutions through molecular assembly. PICET involves a symmetry-breaking charge separation-induced localized charge-separated state, transitioning to a delocalized charge-separated state, which governs the efficiency of •OH generation. Thanks to the oxygen-independent nature of •OH generation and its robust oxidative properties, the ANOR-Cy5-based photosensitizer demonstrates highly effective photoinduced anti-cancer effects, even under severely hypoxic conditions. This discovery emphasizes the potential for achieving •OH photogeneration using a single organic molecule through the engineering of molecular self-assembly, thereby opening up new possibilities for phototherapy and beyond.