79103 20240116083604.0 doi 10.1016/j.actbio.2016.09.041 sideral 97002 ART-2017-97002 eng Casciaro, Bruno Gold-nanoparticles coated with the antimicrobial peptide esculentin-1a(1-21)NH2 as a reliable strategy for antipseudomonal drugs 2017 Access copy available to the general public Unrestricted Naturally occurring antimicrobial peptides (AMPs) hold promise as future therapeutics against multidrug resistant microorganisms. 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 biofilm forms of the bacterial pathogen Pseudomonas aeruginosa. However, bringing AMPs into clinics requires to overcome their low stability, high toxicity and inefficient delivery to the target site at high concentrations. Importantly, peptide conjugation to gold nanoparticles (AuNPs), which are among the most applied inorganic nanocarriers in biomedical sciences, represents a valuable strategy to solve these problems. Here we report that covalent conjugation of Esc(1-21) to soluble AuNPs AuNPs@Esc(1-21)] via a poly(ethylene glycol) linker increased by ~15-fold the activity of the free peptide against the motile and sessile forms of P. aeruginosa without being toxic to human keratinocytes. Furthermore, AuNPs@Esc(1-21) resulted to be significantly more resistant to proteolytic digestion and to disintegrate the bacterial membrane at very low concentration (5 nM). Finally, we demonstrated for the first time 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 treatment 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 via 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. info:eu-repo/grantAgreement/EC/FP7/239931/EU/Multifunctional Magnetic Nanoparticles: Towards Smart Drugs Design/NANOPUZZLE info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-2-R info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 6.383 2017 MATERIALS SCIENCE, BIOMATERIALS 3 / 33 = 0.091 2017 Q1 T1 ENGINEERING, BIOMEDICAL 4 / 77 = 0.052 2017 Q1 T1 1.967 2017 Biochemistry 2017 Q1 Biomaterials 2017 Q1 Biomedical Engineering 2017 Q1 Biotechnology 2017 Q1 Medicine (miscellaneous) 2017 Q1 Molecular Biology 2017 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Moros, Maria (orcid)0000-0002-2861-2469 Rivera-Fernández, Sara (orcid)0000-0003-0616-4383 Bellelli, Andrea Fuente, Jesús M. de la Universidad de Zaragoza (orcid)0000-0003-1081-8482 Mangoni, María Luisa 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica 47 (2017), 170-181 Acta Biomater. ACTA BIOMATERIALIA 1742-7061 5401027 http://zaguan.unizar.es/record/79103/files/texto_completo.pdf Postprint 50257 http://zaguan.unizar.es/record/79103/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:79103 articulos driver 2024-01-16-08:32:18 ARTICLE