Naturally occurring anti
microbial peptides (AMPs) hold pro
mise as future therapeutics against
multidrug resistant
microorganis
ms. Recently, we have discovered that a derivative of the frog skin AMP esculentin-1a, Esc(1-21), is highly potent against both free living and biofil
m for
ms of the bacterial pathogen
m>Pseudomonas aeruginosa.m> However, bringing AMPs into clinics requires to overco
me their low stability, high toxicity and inefficient delivery to the target site at high concentrations. I
mportantly, peptide conjugation to gold nanoparticles (AuNPs), which are a
mong the
most applied inorganic nanocarriers in bio
medical sciences, represents a valuable strategy to solve these proble
ms. Here we report that covalent conjugation of Esc(1-21) to soluble AuNPs [AuNPs@Esc(1-21)]
m>viam> a poly(ethylene glycol) linker increased by &si
m;15-fold the activity of the free peptide against the
motile and sessile for
ms of
m>P. aeruginosam> without being toxic to hu
man keratinocytes. Further
more, AuNPs@Esc(1-21) resulted to be significantly
more resistant to proteolytic digestion and to disintegrate the bacterial
me
mbrane at very low concentration (5 nM). Finally, we de
monstrated for the first ti
me the capability of peptide-coated AuNPs to display a wound healing activity on a keratinocytes
monolayer. Overall, these findings suggest that our engineered AuNPs can serve as attractive novel biological-derived
material for topical treat
ment of epithelial infections and healing of the injured tissue.
Statement of Significance
Despite conjugation of AMPs to AuNPs represents a worthwhile solution to face some limitations for their development as new therapeutics, only a very limited number of studies is available on peptide-coated AuNPs. Importantly, this is the first report showing that a covalent binding of a linear AMP m>viam> a poly(ethylene glycol) linker to AuNPs highly enhances antipseudomonal activity, preserving the same mode of action of the free peptide, without being harmful. Furthermore, AuNPs@Esc(1-21) are expected to accelerate recovery of an injured skin layer. All together, these findings suggest our peptide-coated AuNPs as attractive novel nanoscale formulation to treat bacterial infections and to heal the injured tissue.