A Multifunctional MOF Heterojunction for Combating Antibiotic Resistance and Promoting Regenerative Immunity
Jiayi Qin, Ke Jiang, Zhining Yuan, Ling Zhang, Banglin Chen
Abstract
The treatment of infected wounds is severely hampered by the dual challenges of antimicrobial resistance (AMR) and a dysregulated immune microenvironment. Here, we report a hierarchically engineered microreactor (SK@hZnO@ZIF-8, SZZ) that confronts both issues through a synergistic strategy. The reactor’s core design lies in its pH-responsive, nanostructured ZIF-8 shell, which functions as a nanoscale gate for the on-demand release of Shikonin (SK) and Zn 2+ exclusively within acidic infection sites. This stimuli-responsive delivery eradicates over 99.9% of Methicillin-resistant Staphylococcus aureus (MRSA) and, critically, circumvents drug resistance, maintaining >95% efficacy over 20 passages. Beyond its bactericidal action, SZZ actively reprograms the host immune response, orchestrating a shift from a pro-inflammatory to a pro-reparative state by promoting M2 macrophage polarization and upregulating anti-inflammatory cytokines (TGF-β, IL-10). This synergistic bactericidal and immunomodulatory activity translates to effective in vivo efficacy, achieving complete infection clearance and tissue regeneration (including 72.4% collagen deposition and enhanced hair follicle formation) within just 7 days. This work presents a therapeutic paradigm where nanoscale gating mechanisms on a microscale platform are harnessed to resolve infection and orchestrate complex biological repair processes.