Effects of the conjugation of the antimicrobial peptide Esc(1-21) to gold-nanoparticles

It has been recently demonstrated that the derivative of the frog skin antimicrobial peptide (AMP) esculentin-1a, Esc(1-21), has a strong microbicidal activity against both the free living and the biofilm forms of the bacterial pathogen Pseudomonas aeruginosa with a membrane-perturbing activity as a plausible mode of action.[1] With the aim to overcome the principal limits for the development of AMPs as new therapeutic agents, such as a low biostability, high toxicity and inefficient delivery to the target site, the conjugation of AMPs to inorganic nanoparticles (NPs), e.g. gold NPs (AuNPs), could represent a valuable solution. We demonstrated that the conjugation of Esc(1-21) to AuNPs via a polyethyleneglycol linker significantly increases the activity of the free peptide against the motile and sessile form of P. aeruginosa, respectively, without being harmful to mammalian cells. Furthermore, our engineered NPs were found to preserve the peptide’s ability to disrupt the bacterial membrane and to retain the peptide’s wound healing activity on a keratinocytes monolayer. Our findings suggest that the conjugation of a linear AMP to inorganic nanocarriers, i.e. AuNPs represents an innovative nanoscale formulation for topical treatment of epithelial infections.