Multifunctional NIR‐Triggered Nanozyme‐Based Microneedles for Synergistic Eradication of MRSA and Enhanced Wound Healing

Abstract Antibacterial drug delivery for Methicillin‐resistant Staphylococcus aureus (MRSA)‐infected wounds faces challenges in reducing oxidative stress, reprogramming the inflammatory microenvironment, and promoting angiogenesis. Herein, a multifunctional near‐infrared (NIR) laser‐induced nanozymes (CTB) by integrating nitric oxide (NO)‐prodrug (BNN6) into a phenolic network of Cu2+‐tannic acid. The CTB nanozymes effectively eradicate MRSA through the synergistic effect of NIR‐triggered NO release and NIR‐induced local hyperthermia. Furthermore, the CTB nanozymes exhibit strong antioxidant, anti‐inflammatory, and angiogenic properties. To treat MRSA‐infected cutaneous wounds, novel microneedle patches (MN@CTB)are further developed by incorporating CTB nanozymes into hyaluronic acid methacrylate. The MN@CTB successfully eradicates bacterial infections, leveraging the synergistic effects of NO release and NIR‐induced local hyperthermia. MN@CTB regulates antioxidative and anti‐inflammatory effects by activating the Nrf‐2/HO‐1 signaling pathways and inhibiting the NF‐κB signaling pathway. Additionally, MN@CTB upregulates the expression of soluble guanylate cyclase (sGC), which further activates the protein kinase G (PKG) signaling pathway to stimulate angiogenesis. Proteomic analysis demonstrated the underlying mechanism by which the MN@CTB mainly reprogrammed the infected wound microenvironment by inhibiting the NF‐κB signaling pathway and activating the VEGF/TGF‐β signaling pathways. It is envisioned that this MN@CTB can work as a highly effective strategy for expediting the healing of MRSA‐infected cutaneous wounds.