H2O2-propelled Janus nanomotor for synergistic treatment of drug-resistant biofilm infections.

In contemporary antibacterial treatment, the inability to effectively penetrate biofilm structures, coupled with the rising prevalence of antimicrobial resistance, significantly compromise the clinical efficacy of antibiotic-based therapies. Herein, we propose a hydrogen peroxide (H2O2)-propelled Janus nanomotor designed to co-deliver vancomycin (Van) and silver ions (Ag⁺), thereby enabling synergistic therapy against refractory biofilm infections. The nanomotor is fabricated by self-assembling Van with FDA-approved biocompatible poloxamer 188 (F68) and tannic acid (TA) to create a Van-loaded nanocarrier, with silver nanoparticles (AgNPs) subsequently deposited on one side to generate the final structure (F68@TA/Van@Ag). Within the acidic biofilm microenvironment, oxygen generated through the catalytic decomposition of H2O2 by asymmetrical AgNPs facilitates autonomous movement, allowing efficient biofilm penetration and achieving a 3.9-fold increase in the effective concentration of Van. Concurrently, Ag⁺ released during decomposition induces oxidative stress within bacterial cells, disrupts membrane integrity, and interferes with DNA replication; these actions collectively enhance biofilm eradication in conjunction with Van treatment. Notably, F68@TA/Van@Ag reprograms macrophages toward pro-inflammatory polarization, thus activating robust antibacterial innate immune responses. Overall, our H2O2-propelled Janus nanomotor F68@TA/Van@Ag demonstrates remarkable antibiofilm properties and immunomodulatory effects while maintaining biocompatibility, offering a promising therapeutic strategy for addressing refractory biofilm infections - particularly those drug-resistant biofilm infections.