As a novel type of
antibiotic alternative,
peptide-based antibacterial drug shows potential application prospects attributable to their unique mechanism for lysing the membrane of pathogenic bacteria. However,
peptide-based antibacterial drugs suffer from a series of problems, most notably their immature stability, which seriously hinders their application. In this study, self-assembling chimeric
peptide nanoparticles (which offer excellent stability in the presence of
proteases and
salts) are constructed and applied to the treatment of
bacterial infections. In vitro studies are used to demonstrate that
peptide nanoparticles NPs1 and NPs2 offer broad-spectrum antibacterial activity and desirable biocompatibility, and they retain their antibacterial ability in physiological
salt environments.
Peptide nanoparticles NPs1 and NPs2 can resist degradation under high concentrations of
proteases. In vivo studies illustrate that the toxicity caused by
peptide nanoparticles NPs1 and NPs2 is negligible, and these nanoparticles can alleviate systemic
bacterial infections in mice and piglets. The membrane permeation mechanism and interference with the cell cycle differ from that of
antibiotics and mean that the nanoparticles are at a lower risk of inducing drug resistance. Collectively, these advances may accelerate the development of
peptide-based antibacterial nanomaterials and can be applied to the construction of supramolecular nanomaterials.