Neutrophil Extracellular Traps‐Inspired Bismuth‐Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections

Abstract Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug‐resistant bacteria, rendering ineffective immune responses and even life‐threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid–catechol interaction, the multifunctional bismuth‐based polypeptide nanonets (PLBA‐Bi‐Fe‐TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid‐functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement‐enhanced high‐contact network‐driven multiple efficiency, PLBA‐Bi‐Fe‐TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic‐resistant bacterial biofilms, while Fe‐TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro‐inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial‐associated infections at all stages through synergetic treatment.