Orchestrating Diabetic Wound Healing by a Sunlight-Activated AIEgen-Selenide Nanospray: From Infection Control to Tissue Regeneration

Diabetic wounds, particularly diabetic ulcers (DUs), are life-threatening complications driven by bacterial infection, persistent inflammation, oxidative stress, and a dysfunctional immune microenvironment. Addressing these interconnected barriers requires a therapeutic strategy capable of coordinating infection control with tissue repair. Here, we report a sunlight-activated nanospray formulation (C@PSe) based on a covalently engineered aggregation-induced emission luminogen (AIEgen)-selenide triblock copolymer micelle that encapsulates curcumin (Cur). This system integrates three complementary functions into a single micellar platform. The AIEgen enables on-demand antimicrobial photodynamic therapy (aPDT) under natural sunlight, achieving precise bacterial elimination. The selenide block exerts glutathione peroxidase (GPx)-like activity to scavenge excess reactive oxygen species (ROS), alleviating oxidative stress and modulating the nuclear factor kappa-B (NF-κB)-associated inflammatory signaling. Simultaneously, Cur promotes anti-inflammatory macrophage polarization and drives pro-angiogenic signaling to support tissue regeneration. In a Staphylococcus aureus-infected diabetic mouse model, C@PSe effectively resolved bacterial infection, reduced ROS-driven inflammation, and accelerated wound closure with full re-epithelialization and enhanced neovascularization. By integrating sequential antibacterial, antioxidant, and regenerative actions within a single, patient-friendly nanospray that operates under sunlight, this platform overcomes key limitations of conventional photodynamic therapy (PDT) and offers a comprehensive strategy for treating chronic diabetic wounds.