pH‐Triggered Size‐Transformable and Bioactivity‐Switchable Self‐Assembling Chimeric Peptide Nanoassemblies for Combating Drug‐Resistant Bacteria and Biofilms

Abstract

Drug‐resistant bacteria and biofilm‐associated infections are prominent problems in the field of antibacterial medicine, seriously affecting human and animal health. Despite the great potential of nanomaterials in the antibacterial field, overcoming the paradox of size and charge, efficient penetration, and retention within biofilms remain a formidable challenge. Here, self‐assembling chimeric peptide nanoassemblies composed of multiple functional fragments are designed for the treatment of drug‐resistant bacteria and biofilm‐associated infections. Notably, the chimeric peptide self‐assembles into nanofibers at pH 7.4 and is transformable into nanoparticles in the acidic biofilm‐infected microenvironment at pH 5.0, and thus achieves a size reduction and charge increase, improving the penetration into the bacterial biofilms and killing drug‐resistant bacteria by a mechanism dominated by membrane cleavage. In vivo mouse and piglet infection models confirm the ability of chimeric peptide nanoassemblies to reduce bacterial load within biofilms. Collectively, this research on pathological‐environment‐driven nanostructural transformations may provide a theoretical basis for designing high‐performance antibacterial nanomaterials and advance the application of peptide‐based nanomaterials in medicine and animal husbandry.

Recent advances in nanomaterial-mediated bacterial molecular action and their applications in wound therapy

“…10A). 143 Nanohole-enriched MoS 2 (NR-MoS 2 ) can act as electronic donors to facilitate electron transport with the biofilms (electronic receptors). Interestingly, biofilm formation was inhibited by electron transport by attacking crucial active sites on the biofilm ( e.g.…”

Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

“…Kidneys and livers of piglets were removed and fixed with 4% paraformaldehyde. Finally, the samples were stained with H&E for histological analysis. , …”

In situ peptide assemblies for bacterial infection imaging and treatment

“…Recently, Ma and co-workers developed a chimeric peptide containing a self-assembling motif C 14 alkyl chain, a pH-responsive and β-sheet domain (HHHF) 4 , a hydrophilic PEG sequence, and a P. aeruginosa -targeting ligand QRKLAAKLT. 102 Remarkably, the acidic environment led to the protonation of histidine residues, triggering the nanofiber-to-nanofiber transformation of the chimeric peptide. As a result, the chimeric peptide reduced its size to efficiently penetrate bacterial biofilms, as well as turned on its positive charge to kill drug-resistant P. aeruginosa .…”