Photothermally-activated nano-delivery system for on-demand treatment of diabetic wound infections

Bacterial-infected diabetic wounds, characterized by a persistent hyperglycemic environment, susceptibility to secondary bacterial infections, and chronic inflammatory responses, often exhibit impaired healing processes, posing a significant challenge in clinical management. To address this issue, this study designed and constructed a near-infrared (NIR) light-activated intelligent hydrogel drug delivery system-LSZBP@CMO. This system integrates highly efficient photothermal conversion components with a pH-responsive CMO hydrogel based on Schiff base reactions, achieving a dual-stimuli responsive drug release mechanism governed by exogenous NIR light and endogenous microenvironmental acidity. Under NIR irradiation, localized mild hyperthermia is generated, leading to the disruption of thermosensitive structures within the system and exposure of nanoparticles. This process, synergizing with the mildly acidic environment, further triggers rapid drug release, significantly enhancing antibacterial efficacy. Both in vitro and in vivo experimental results demonstrated that LSZBP@CMO not only efficiently eliminates bacteria but also effectively alleviates oxidative stress, modulates the inflammatory microenvironment, and markedly promotes angiogenesis, collagen deposition, and epithelial regeneration. In a diabetic rat model with infected wounds, the treatment group exhibited outstanding repair performance, achieving a wound healing ratio of 97.39 ± 1.60 % by day 7. This study provides an actively controllable strategy with promising clinical application prospects for on-demand therapy of refractory bacterial-infected diabetic wounds.