Abstract
Diabetic wounds are among the most challenging complications of diabetes, particularly when persistent bacterial biofilms sustain infection, oxidative stress, and inflammation. Here, we developed an infection-microenvironment-responsive nanotherapeutic platform (AuNCs@PGD) by associating guanidine-rich PGD polymers with gold nanoclusters (AuNCs). The cationic PGD coating promotes interaction with negatively charged bacterial and biofilm components, while phenylboronic-acid motifs provide additional affinity for diol-containing surface glycoconjugates. Under 808-nm irradiation, AuNCs@PGD produced a reproducible photothermal response and, together with bacterial capture and membrane disruption, markedly reduced bacterial viability and biofilm burden in vitro. In a polymicrobial diabetic full-thickness wound model, AuNCs@PGD2 + NIR accelerated wound closure and was associated with reduced bacterial burden, lower ROS/MDA and inflammatory cytokine levels, increased collagen deposition, and enhanced CD31-positive neovascularization. Overall, AuNCs@PGD integrates bacterial localization, photothermal antibacterial activity, and redox modulation in a single platform for infected diabetic wound treatment.