pH/H2O2 dual-responsive macrophage-targeted chitosaccharides nanoparticles to combat intracellular bacterial infection

Abstract

Antibiotic resistance combined with bacteria internalization result in recurrent infections that seriously threaten human health. To overcome these problems, a pH/H₂O₂ dual-responsive nanoparticle (COSBN@CFS@PS) that can target macrophages, exhibiting synergistic antibiotic and β-lactamase inhibitor activity, is reported. Chitosaccharides (COS) is covalently bound with benzenboronic acid pinacol ester and assemble with cefoxitin sodium salt (CFS) to form COSBN@CFS nanoparticles. Then, COSBN@CFS was encapsulated with phosphatidylserine (PS), which aimed to targeted uptake by macrophages. After the uptake, the pH/H₂O₂ dual-responsive nanoparticle could effectively inhibit β-lactamase activity by release boronic acid (β-lactamase inhibitor), and then reinforced the antibacterial activity of CFS. Meanwhile, the resultant nanoparticles could significantly inhibit the growth of CFS-resistant bacteria. Furthermore, these nanoparticles could eliminate intracellular bacteria in vivo through the synergistic activities of antibiotic and β-lactamase inhibitor. The excellent biocompatibility and outstanding bactericidal activity promise COSBN@CFS@PS have great potential for diverse intracellular bacterial infection therapy.

Keywords: Bactericidal activity; Intracellular infection; Macrophage-targeted nanoparticle; Synergistic activity; β-lactamase inhibitor.