Zhihui Zhang, Yu Zhang, Bosong Zhou, Peilu Huang, Qi Zhang, Zhi Xu, Xu Wu, Xianglin Dong, Lei Wang, Ruiyuan Liu
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.