Macrophage-Inspired Fe3O4 Nanozymes with a Hydrophobic Spiky Topography for Treating Drug-Resistant Bacteria

Abstract Fe3O4, the first reported nanozyme and the first FDA-approved transition-metal-based nanomaterial, holds promise for antibacterial therapy but is limited by poor ROS catalytic activity and utilization. Inspired by macrophage-like bacterial capture and insect wing micro/nanostructures, we designed Fe3O4 nanoparticles encapsulated in a conductive, hydrophobic carbon shell with densely aligned nanoneedles. This architecture shifted the Fe/O d/p-band centers toward the Fermi level, promoted H2O2 adsorption and activation, and strengthened H2O2 homolysis through H2O2–O hydrogen bonding, yielding 2.67-fold higher POD-like activity than that of pristine Fe3O4. The hydrophobic nanoneedle surface further inhibited continuous liquid film formation, enhanced bacterial adhesion, and shortened the distance between ROS generation sites and bacterial membranes, thereby improving ROS utilization. Consequently, the engineered Fe3O4 nanozyme achieved an MRSA inhibitory concentration nearly 15-fold lower than pristine Fe3O4. This work offers a microenvironment engineering strategy to advance Fe3O4-based antibacterial nanozymes toward clinical translation.