A Sulfur-Modified Cryptolepine-Based Type I/II AIE Photosensitizer for Efficient Eradication of Planktonic Bacteria and Biofilms

Abstract In recent years, the application of aggregation-induced emission photosensitizers (AIE PSs) in photodynamic therapy has gained significant traction as an effective approach for eradicating bacteria and biofilms. We developed a series of AIE PSs based on structural modifications of the natural product cryptolepine. Among them, TPA-CRYS exhibited exceptional type I/II reactive oxygen species (ROS) generation capability. At a low concentration of 20 nM, TPA-CRYS exerted potent antibacterial activity, achieving over 99.7% eradication of both Staphylococcus aureus and MRSA. Notably, TPA-CRYS effectively inhibited biofilm formation but also disrupted established biofilms. Mechanistic investigations revealed that the bactericidal action ofs TPA-CRYS stems from a synergistic combination of bacterial membrane disruption and intracellular ROS-mediated oxidative damage. Furthermore, TPA-CRYS showed good biocompatibility with mammalian cells. Most importantly, TPA-CRYS exhibited outstanding therapeutic performance in a mouse wound infection model. This study presents a promising natural product-derived AIE PS and a novel strategy for treating bacterial infections.