Photoinitiator based on oxime ester for photodynamic antibacterial therapy and wound healing

Bacterial infections significantly impede wound healing and threaten global public health. Although photodynamic therapy (PDT) has emerged as a promising antibiotic-free antibacterial strategy, the hypoxic condition within biofilms has limited the clinical effectiveness of conventional oxygen-dependent PDT. Herein, we designed and prepared a novel type I/II dual-mechanism and oxygen-independent aryl free radical combined oxime ester based photoinitiator (DPTO) for treating bacterial infections and enhancing wound healing. Upon white light irradiation, DPTO generates type I and type II ROS (¹O₂, O₂•^-, and •OH) via photodynamic process. Additionally, DPTO undergoes photolysis to produce oxygen-independent aryl free radical. Particularly, DPTO could accumulate in the mitochondria, boost mitochondrial radicals, and damage mitochondria. The combined generation of type-I/II ROS and aryl free radicals confers potent in vitro antibacterial activity. Crucially, significant in vivo therapeutic efficacy was validated in a rat wound infection model. In summary, our study not only validates the substantial potential of DPTO in photodynamic antibacterial therapy but also provides a foundation for developing efficient oxime ester based photoinitiator for the treatment of bacterial infections.