Lukui Chen, Dawei Liang, Yi Qin, Lu He, Shuxian Li, Mengyi Cai, Yilan Tan, Jingjing Liang, Zhili Li, Lei Zheng, Jing Zhang, Mengchen Zou
Diabetic foot ulcers (DFUs) complicated by multidrug-resistant (MDR) bacterial infection present a significant clinical challenge that necessitates innovative therapeutic strategies. Conventional antimicrobial treatments often fail because of limited tissue penetration, antibiotic resistance, and poor efficacy against biofilm-forming pathogens. In this study, we developed a near-infrared (NIR) light-responsive aggregation-induced emission luminogen (AIEgen) with high photothermal conversion efficiency, excellent photostability, and favorable biocompatibility. Upon NIR light activation, this AIEgen can induce localized hyperthermia capable of disrupting bacterial membranes and penetrating deep into infected tissues, thereby effectively eradicating the embedded MDR pathogens and resilient biofilms. The antibacterial efficacy of the AIEgen was validated against MDR clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). In vitro and in vivo evaluations confirmed the potent bactericidal activity, efficient biofilm disruption ability, and minimal cytotoxicity of the AIEgen. Notably, in a DFU infection model, AIEgen administration and NIR light exposure significantly accelerated wound healing by eliminating pathogens, suppressing inflammation, promoting M2 macrophage polarization, enhancing collagen deposition, and stimulating angiogenesis. In conclusion, this AIEgen-based photothermal system offers a noninvasive, biocompatible, and deeply penetrating antibacterial strategy for the treatment of chronic MDR infections in DFUs and has great potential for clinical translation.