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 <i>Staphylococcus aureus</i> and <i>Salmonella typhimurium</i>, 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.