Cationization-Enhanced Type I and Type II ROS Generation for Photodynamic Treatment of Drug-Resistant Bacteria

Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in an aggregate and hypoxic microenvironment. Herein, we report a molecular cationization approach to boost the ROS, especially type I ROS generation of aggregation-induced emission (AIE) photosensitizers for photodynamic treatment of drug-resistant bacteria. Such cationization reinforces the electron-accepting ability of the cationic moiety, promotes intersystem crossing (ISC), and increases electron separation and transfer processes. The resultant <b>CTBZPyI</b> exhibits largely enhanced ROS generation ability with predominant hydroxyl radical generation over its neutral counterpart in aggregate. Moreover, cationization also confers <b>CTBZPyI</b> with the bacterial binding ability and a moderate bacterial inactivation ability in the dark. Further light irradiation leads to superb antibacterial performance, which largely promotes the healing process of a <i>MRSA</i>-infected wound. Such a cationization strategy is expected to be a general strategy for the design of highly effective type I photosensitizers for bacterial infection treatment.