Organic Heterojunction Nanoparticles: Photoinduced Charge Transfer and Melanin-Amplified ROS Generation for Melanoma Photodynamic Therapy

High Resolution Image Download MS PowerPoint Slide Melanoma is a life-threatening cancer, requiring more effective treatments. Photodynamic therapy (PDT) is a promising approach with favorable biosafety, although its clinical efficacy remains limited. In this work, we developed a nanoplatform combining poly(9,9-dioctylfluorene- alt -benzothiadiazole) (PFBT) and 1-[3-(methoxycarbonyl)propyl]-1-phenyl-[6.6]C 61 (PCBM), forming PFBT/PCBM (PP) nanoparticles, which contain a type II heterojunction that enables efficient charge transfer (≥97.7%) under irradiation. The resulting PFBT +• and PCBM –• radicals enable the generation of diverse reactive oxygen species (ROS) at high levels, including superoxide, hydroxyl radicals, and singlet oxygen (both type I and II ROS), through efficient electron and hole transfer processes. These multiple ROS species culminate in potent antitumor activity in vitro and in melanoma-bearing mice. Importantly, endogenous melanin accelerated the photocatalytic cycle, further amplifying the generation of ROS, thus enhancing the therapeutic outcome. Furthermore, PP-based PDT also demonstrated promising results in combating postsurgical infection and supporting wound healing, highlighting its potential as a multifunctional tool for comprehensive melanoma management. This work presents a PFBT/PCBM (PP) nanoplatform formed by coassembling poly(9,9-dioctylfluorene- alt -benzothiadiazole) (PFBT) and PCBM to achieve highly efficient photoinduced charge transfer efficiency (≥97.7%). The resulting PFBT +• and PCBM –• radicals enable the generation of diverse reactive oxygen species (ROS) at high levels, while endogenous melanin accelerates the photocatalytic cycle, further amplifying the generation of ROS and enhancing the therapeutic outcome.