Infection microenvironment-responsive guanidine-modified nanostructures for precision photothermal therapy of diabetic wounds.

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.