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

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.