Engineering magnetically guided bacteriophages for precision antimicrobial therapy and targeted biofilm eradication

Viruses, including bacteriophages, rely on passive diffusion to reach their hosts, limiting the efficacy of virus-based therapies and leading to off-target accumulation with systemic effects. Here, we present a strategy to confer controllable motility to bacteriophages by incorporating iron nanoparticles (FeNPs) into their head structures while preserving infectivity. Cryo-electron microscopy (Cryo-EM) and transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS) confirmed the FeNP presence in the phages head. FeNP-tagged phages can be magnetically enriched and isolated from bacterial prey cultures, eliminating the need for ultracentrifugation. Under magnetic guidance, these engineered phages exhibit rapid and directed movement through complex microenvironments, including mazes and polymer barriers, enabling precise bacterial targeting and biofilm eradication in a microfluidic system. In an in vivo wound infection model, magnetically guided phages successfully navigated from the peritoneum to the biofilms on the wound, thus selectively eliminating biofilms while minimizing systemic exposure to other organs. Hence, our approach confers viral mobility, thus enhancing the precision and efficacy of bacteriophage-based biotechnological and therapeutic applications.