Charge-Transfer-Coupled J-Aggregation Enhances ROS Generation via Efficient Intermolecular Electron Transfer for Photodynamic Therapy

Aggregation engineering of organic photosensitizers (PSs) is a promising strategy to enhance reactive oxygen species (ROS) production for photodynamic therapy (PDT). However, current approaches primarily rely on traditional long-range coulomb-coupled J-aggregate (J_C) that exhibit suboptimal Type II ROS production and weak intermolecular electron transfer (InterET), which is unfavorable for Type I ROS generation. Here, we report a charge-transfer (CT)-coupled J-aggregates (J_CT) as efficient organic PS (BDR NPs) to significantly enhance both Type I and Type II ROS production for superior PDT. Unlike traditional J_C-aggregates, J_CT -aggregates exhibit both accelerated intersystem crossing for improved Type II ROS generation and enlarged intermolecular orbital overlap that promotes efficient InterET for Type I ROS production. Therefore, BDR NPs achieve 8.2- and 4.1-fold increases in superoxide (O₂⁻•) and hydroxyl radical (•OH) production, respectively, compared with its J_C-counterparts. Notably, BDR NPs exhibit an over 2-fold higher production of O₂⁻• and •OH compared with commercial PS Rose Bengal, achieving markedly accelerated wound healing. This superior PDT efficacy arises from the synergistic suppression of inflammation and activation of tissue regeneration. This work elucidates the mechanistic basis of J_CT-aggregate in enhancing ROS production, offering a foundational framework for designing high-performance PSs.