Macrophage Polarization Induced by Bacteria-Responsive Antibiotic-Loaded Nanozymes for Multidrug Resistance-Bacterial Infections Management

Abstract

Inherited bacterial resistance and biofilm-induced local immune inactivation are important factors in the failure of antibiotics to fight against bacterial infections. Herein, antibiotic-loaded mesoporous nanozymes (HA@MRuO₂ -Cip/GOx) are fabricated for overcoming bacterial resistance, and activating the local immunosuppression in biofilm microenvironment (BME). HA@MRuO₂ -Cip/GOx are prepared by physical adsorption between ciprofloxacin (Cip) or glucose oxidase (GOx) and MRuO₂ NPs, and modified with hyaluronic acid (HA). In vitro, HA@MRuO₂ -Cip/GOx cleaves extracellular DNA (eDNA) to disrupt biofilm, thereby enhancing Cip kill planktonic bacteria. Furthermore, HA@MRuO₂ -Cip/GOx can induce polarization and enhance phagocytosis of a macrophage-derived cell line. More importantly, in vivo therapeutic performance confirms that HA@MRuO₂ -Cip/GOx can trigger macrophage-related immunity, and effectively alleviate MRSA-bacterial lung infections. Accordingly, nanocatalytic therapy combined with targeted delivery of antibiotics could enhance the treatment of bacterial infections.

Keywords: antibiotics; bacterial infections; biofilms; macrophages; nanozymes.