Biomimetic Macrophage–Fe3O4@PLGA Particle-Triggered Intelligent Catalysis for Killing Multidrug-Resistant Escherichia coli

Abstract

Infections with multidrug-resistant (MDR) Gram-negative bacteria, such as MDR Escherichia coli (E. coli), remain a challenge due to the lack of safe antibiotics and high fatality rates under anti-infection therapies. This work presents a form of biomimetic intelligent catalysis inspired by the selective biocatalytic property of macrophages (MΦs), consisting of an intelligent controlling center (a living MΦ) and a Fenton reaction catalyst (Fe3O4@poly(lactic-co-glycolic acid) (PLGA) nanoparticles) for killing MDR E. coli without harming normal cells. The MΦ–Fe3O4@PLGA particles (i.e., the intelligent catalysis particles) exhibit selective biocatalysis activity toward MDR E. coli by producing H2O2 and lipid droplets (LDs). This process activates the lipid metabolism and glycan biosynthesis and metabolism pathways based on the result of RNA sequencing data analysis. The H2O2 further reacts with Fe3O4@PLGA to form highly toxic hydroxyl radicals (·OH), while the LDs contain antimicrobial peptides and can target MDR E. coli. The highly toxic ·OH and antimicrobial peptides are shown to combat with MDR E. coli, such that the antibacterial efficiency of the MΦ–Fe3O4@PLGA particles against MDR E. coli is 99.29% ± 0.31% in vitro. More importantly, after several passages, the intelligent catalysis function of the MΦ–Fe3O4@PLGA particles is well maintained. Hence, the concept of biomimetic intelligent catalysts displays potential for treating diseases other than infections.