Ultrasmall Self-Cascade Bimetallic Au2Pd3 Nanozymes Encapsulated Hydrogel Microneedles for Photothermal-Augmented Nanocatalytic Therapy of Diabetic Wound Infections.

An ultrasmall bimetallic Au2Pd3 nanozyme with self-cascade enzyme-like activities and robust photothermal heating properties is synthesized and encapsulated into a poly(vinyl alcohol)/hyaluronic acid (PVA/HA) matrix via a repeated freezing and thawing process to yield a hydrogel microneedle patch (Au2Pd3@PH). This microneedle displays a good tissue-piercing capability and thermal-responsive melting behavior. Upon exposure to an 808 nm near-infrared laser, Au2Pd3@PH dissolves and releases Au2Pd3, which shows glucose oxidase (GOx)-like catalytic activity for the conversion of endogenous glucose into gluconic acid and hydrogen peroxide (H2O2), thereby reducing the glucose level and local pH at the wound site. The reduced pH induces the peroxidase-like activity of Au2Pd3 to further oxidize H2O2 into the hydroxyl radical (•OH). In vitro experiments reveal that Au2Pd3@PH exhibits antibacterial rates exceeding 99% against both Staphylococcus aureus and Salmonella typhimurium, showing a photothermal/chemodynamic dual-mode synergistic antibacterial effect. Further in vivo assays demonstrate that the Au2Pd3@PH treatment group achieves near-complete healing of infected diabetic wounds within 7 days, indicating an enhanced wound healing process. The treatment with Au2Pd3@PH effectively modulates inflammatory factor expression, including marked downregulation of TNF-α and IL-6, while simultaneously promoting collagen deposition and angiogenesis, with no adverse biological effects observed. Therefore, the proposed Au2Pd3@PH hydrogel microneedle provides a promising strategy for treating diabetic wound infections with a high performance.