A Cascade Catalytic Nanoplatform Enabling PTT/CDT Synergistic Antibacterial and Heat-Triggered NO Release for Angiogenesis in Diabetic Wound Healing.

Hyperglycemia-associated infection susceptibility impairs wound healing, and achieving coordinated regulation of infection control and tissue regeneration remains a major challenge. To address this, a cascade catalytic nanoplatform (CT@CB@Dex) integrating antibacterial and pro-angiogenic functions was constructed. Copper-based nanosheets were synthesized as a photothermal catalytic core, followed by electrostatic adsorption of CeO2 nanozymes to form CT@C, loading of a NO donor (BNN6) via electrostatic interaction to obtain CT@CB, and finally dextran coating for improved biocompatibility and biofilm targeting. This system enables synergistic therapy via photothermally enhanced chemodynamic therapy (CDT) and NO release. Dextran modification enables targeted accumulation and prolonged retention within biofilm regions. Subsequently, a cascade-amplified CDT is achieved: CeO2 nanozymes convert superoxide radicals into H2O2 via SOD-like activity, providing substrates for Cu2+-mediated Fenton-like reactions to continuously generate ·OH, thereby exerting potent antibacterial effects. Upon near-infrared (NIR) irradiation, the nanoplatform exhibits strong photothermal conversion performance. The strong photothermal heating not only accelerates catalytic reactions to enhance CDT but also triggers thermal decomposition of BNN6 for controlled NO release, which promotes angiogenesis. In vitro, CT@CB@Dex exhibits broad-spectrum antibacterial and anti-biofilm activity, with bacterial survival below 3% against E. coli and S. aureus. Meanwhile, NO treatment increases VEGF and bFGF expression, accompanied by enhanced endothelial cell migration and tube formation. In vivo, CT@CB@Dex achieved 99.03 ± 0.32% wound closure on day 14 under NIR irradiation, accompanied by reduced inflammation, enhanced collagen deposition, and improved angiogenesis. Overall, this multifunctional nanoplatform integrates antibacterial, anti-biofilm, and pro-angiogenic functions, offering a promising strategy for diabetic wound treatment.