Targeting the limitation of antimicrobial peptides (AMPs)
application in vivo, self-assembled AMPs library
with specific nanostructures
is expected to gradually overtake monomer AMPs libraries in the future.
Peptide polymers are fascinating self-assembling nanoscale structures
that have great advantage in biomedical applications because of their
satisfactory biocompatibility and versatile properties. Herein, we
describe a strategy for inducing the self-assembly of T9W into nanostructured
antimicrobial micelles with evidently improved pharmacological properties,
that is, PEGylation at the C-terminal of T9W (CT9W1000),
an antibacterial biomaterial that self-assembles in aqueous media
without exogenous excipients, has been developed. Compared with parental
molecular, the CT9W1000 is more effective against Pseudomonas aeruginosa, and its antibacterial spectrum
had also been broadened. Additionally, CT9W1000 micelles
had higher stability under salt ion, serum, and acid–base environments.
Importantly, the self-assembled structure is highly resistant to trypsin
degradation, probably allowing T9W to be applied in clinical settings
in the future. Mechanistically, by acting on membranes and through
supplementary bactericidal mechanisms, CT9W1000 micelles
contribute to the antibacterial process. Collectively, CT9W1000 micelles exhibited good biocompatibility in vitro and in vivo, resulting in highly effective treatment
in a mouse acute lung injury model induced by P. aeruginosa PAO1 without drug resistance. These advances may profoundly accelerate
the clinical transformation of T9W and promote the development of
a combination of peptide-based antibiotics and PEGylated nanotechnology.
The nonapeptides 3IW (RIRIRIRWL-NH2) and W2IW (RWRIRIRWL-NH2) based on a β-pleated sheet template have potent broad-spectrum antimicrobial effects via membrane disruption and ROS accumulation, and show favorable preservative effects in chicken meat.
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