Ultrasmall Self-Cascade Bimetallic Au 2 Pd 3 Nanozymes Encapsulated Hydrogel Microneedles for Photothermal-Augmented Nanocatalytic Therapy of Diabetic Wound Infections

An ultrasmall bimetallic Au 2 Pd 3 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 (Au 2 Pd 3 @PH). This microneedle displays a good tissue-piercing capability and thermal-responsive melting behavior. Upon exposure to an 808 nm near-infrared laser, Au 2 Pd 3 @PH dissolves and releases Au 2 Pd 3, which shows glucose oxidase (GOx)-like catalytic activity for the conversion of endogenous glucose into gluconic acid and hydrogen peroxide (H 2 O 2 ), thereby reducing the glucose level and local pH at the wound site. The reduced pH induces the peroxidase-like activity of Au 2 Pd 3 to further oxidize H 2 O 2 into the hydroxyl radical ( • OH). In vitro experiments reveal that Au 2 Pd 3 @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 Au 2 Pd 3 @PH treatment group achieves near-complete healing of infected diabetic wounds within 7 days, indicating an enhanced wound healing process. The treatment with Au 2 Pd 3 @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 Au 2 Pd 3 @PH hydrogel microneedle provides a promising strategy for treating diabetic wound infections with a high performance.