Cationic AIE-active photosensitizers for highly efficient photodynamic eradication of drug-resistant bacteria

Abstract

Drug-resistant bacteria present a grave threat to human health. Photodynamic therapy (PDT) holds enormous potential as an innovative treatment in antimicrobial therapy. However, the generation of reactive oxygen species (ROS) for traditional photosensitizers in a hypoxic microenvironment or aggregated state is always restricted, limiting the antimicrobial effect. Herein, a cationization and cyano introduction molecular engineering strategy is reported to develop aggregation-induced emission active photosensitizers with enhanced type I ROS generation and bacteria binding ability for successful drug-resistant bacteria eradication. The introduction of a cyano group improves the light harvesting ability and ROS generation. This cationization can convert neutral molecules (TPAQ and CN-TPAQ) to their cationic counterparts (TPAQ-PF₆ and CN-TPAQ-PF₆), and enhance electron separation as well as transfer processes, which further promotes the ROS generation capacity, and in particular highly toxic hydroxyl radicals in aggregates that are 5.4-fold stronger than commercial crystal violet (CV) can be produced. As both the cationic charge and cyano group possess excellent bacterial binding affinity, the cationic CN-TPAQ-PF₆ shows an excellent photodynamic killing efficiency of >99.999999% toward MRSA and >99.99999% toward S. aureus respectively at a very low concentration (2 μM) and under low intensity daylight exposure (40 mW cm⁻²), and the antibacterial performance is superior to that of clinical vancomycin antibiotics. Furthermore, CN-TPAQ-PF₆ is also successfully applied in bacteria sterilization in natural lake water. This work provides a powerful guide for the appropriate design of novel and efficient type I AIE PSs to effectively conquer antibiotic resistance.