Dendritic Cell-Inspired Triple-Functional Biocatalysts with Atomic Iron Sites To Eradicate Drug-Resistant Bacteria and Biofilms.

Abstract

The global crisis of antimicrobial resistance demands solutions that transcend conventional antibiotic paradigms. Here, we present an atomically engineered VS₄-based nanomaterial (TFB-Fe@VS₄) featuring dendritic architectures with single-iron catalytic sites, designed as a multimodal reactive oxygen species (ROS) generator against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and its recalcitrant biofilms. This biocatalytic system leverages three synergistic mechanisms: nanodendrite-mediated bacterial capture, microenvironment-responsive ROS generation, and ultrasound-amplified oxidative burst, which collectively address the key challenges in eradicating drug-resistant infections. Structural and spectroscopic analyses reveal that atomic iron sites serve dual functions as peroxidase-mimetic catalytic sites and electronic structure modulators, significantly enhancing ultrasound-triggered ROS production through band engineering. The TFB-Fe@VS₄ achieves complete MRSA biofilm eradication and rapid wound sterilization in rabbit models with therapeutic outcomes similar to vancomycin yet without detectable inflammation or systemic toxicity. These findings present a design example for artificial biocatalysts that combines precise atomic engineering with multimodal antimicrobial action. The ability to simultaneously target bacterial adhesion, microenvironment adaptation, and on-demand ROS amplification presents transformative potential for treating resistant infections across diverse clinical scenarios, particularly where conventional therapies fail.