Bacteria‐responsive transformable peptide‐based nanomaterials inspired by human α‐defensin 6 for labeling and entrapping pathogenic bacteria

Abstract Antimicrobial resistance caused by overuse of antibiotics has promoted the demand for effective antibacterial materials. However, the development of existing antibacterial strategies mostly focuses on direct sterilization, which may lead to flora imbalance and drug resistance. Here, a series of peptide‐based aggregation‐induced emssion nanomaterials (PBANs) with multiple structural domains were designed by mimicking the self‐assembly of human α‐defensin 6. Specifically, PBANs self‐assemble to form nanoparticles in physiological environments and in situ transform into nanofibers on bacterial surfaces through receptor‐ligand interactions in infected microenvironments, resulting in enhanced fluorescence signal and activation of functions, while labeling and entrapping bacteria. Different from traditional antibacterial strategies that directly kill pathogenic microorganisms, PBANs can inhibit bacterial motility and invasion into the host system through physical barriers and affecting energy metabolism pathways. In addition, PBANs can further recruit macrophages to the infection site to engulf entrapped bacteria, thereby synergistically reducing the infection efficiency. In mouse and piglet systemic infection models, the PBANs showed favorable therapeutic efficacy, significantly reducing bacterial load and levels of inflammation factors. Overall, this study provides perspectives for developing biomimetic stimuli‐responsive nanomaterials to combat bacterial infections.