Sunlight-Triggered Bacterial Membrane-Targeting Aggregation-Induced Emission “Nanoantibiotic” Hydrogel for Ultrafast Multidrug-Resistant Bacteria Eradication and Diabetic Wound Healing

Abstract Drug-resistant bacterial infections and persistent biofilm formation pose critical bottlenecks for diabetic wound management. To overcome these challenges, a sunlight (SL)-triggered aggregation-induced emission (AIE) photosensitizer, designated as MTP, was engineered and incorporated into an injectable thermosensitive hydrogel. Featuring a donor–acceptor architecture, MTP exhibits NIR fluorescence emission, while its visible light absorption enables sunlight-triggered dual-type photodynamic activity. Crucially, MTP achieves ultrafast bacterial cell membrane anchoring within 15 seconds, delivering exceptional bactericidal efficacy under natural solar power light. At a concentration of 30 nM, it eradicates Gram-positive pathogens and profoundly dismantles mature, multidrug-resistant biofilms. Transcriptomic and biochemical analyses revealed that the photodynamically generated reactive oxygen species (ROS) burst triggers a lethal damage cascade. This process induces severe membrane lipid peroxidation, transmembrane transport dysfunction, and complete collapse of intracellular proteostasis. During in vivo evaluations, the highly biocompatible composite hydrogel dramatically accelerated tissue regeneration in a methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic mouse model. Sunlight activation contracted the wound area to 35.5% by day 6 compared to 87.4% for the untreated control, achieving therapeutic efficacy on par with that of clinical vancomycin while favorably modulating the local inflammatory microenvironment. Ultimately, this nonantibiotic platform offers a highly effective and mechanism-clarified strategy for combating refractory wound infections with excellent biocompatibility.