Precise Molecular Engineering of Type I Photosensitizers with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Killing of Multidrug-Resistant Bacteria

Multidrug resistance (MDR) bacteria pose a serious threat to human health. The development of alternative treatment modalities and therapeutic agents for treating MDR bacteria-caused infections remains a global challenge. Herein, we rationally designed and successfully developed a series of near-infrared (NIR) anion-π+ photosensitizers featuring aggregation-induced emission (AIE-PSs) for broad-spectrum MDR bacteria eradication. Due to the strong intramolecular charge transfer (ICT) and enhanced highly efficient intersystem crossing (ISC), these electron-rich anion-π+ AIE-PSs showed boosted type I reactive oxygen species (ROS) generation capability involving hydroxyl radicals and superoxide anion radicals, and up to 99% photodynamic killing efficacy was achieved for both Methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Escherichia coli (MDR E.coli) under a low dose white light irradiation (16 mW cm-2). In vivo experiments confirmed that one of these AIE-PSs exhibited excellent therapeutic performance in curing MRSA or MDR E.coli-infected wounds with negligible side-effects. The study would thus provide useful guidance for the rational design of high-performance type I AIE-PSs to overcome antibiotic resistance.