Photogeneration of Hydroxyl Radicals Based on Aggregation-Induced Emission Luminogen-Assembled Copper Cysteamine Nanoparticles for Photodynamic Therapy

Hydroxyl radical (•OH) is regarded as the most aggressive reactive oxygen species and can react directly with various vital biomacromolecules. Therapeutic strategies based on •OH generation have been used as a prospective method to boost anticancer efficiency. Herein, the heterogeneous nanoplatform (NSCuCy) was constructed via a feasible assembly process involving AIE active type-I photosensitizers NS-STPA and copper cysteamine (CuCy) nanoparticles (NPs). Upon 660 nm laser irradiation, NS-STPA effectively produced superoxide anion (•O2–) through type-I photodynamic therapy (PDT). The introduction of Cu+-dominated CuCy actualizes the Fenton catalyst to accelerate the transformation of •O2– into •OH. Meanwhile, the •OH generation from NSCuCy NPs showed more hypoxia-tolerance and is acidic favorable. After tail intravenous injection, the NSCuCy NPs accumulated in the tumor site and achieved total tumor ablation through CuCy-facilitated type-I PDT and •OH generation upon 660 nm irradiation. This strategy inspired further exploration of theranostic nanoplatforms with •OH-generated type-I PDT for potential clinical translation.