title: One-step synthesis of high-density peptide-conjugated gold nanoparticles with antimicrobial efficacy in a systemic infection model.
abstract: The increase in antibiotic drug resistance and the low number of new antibacterial drugs approved in the last few decades requires the development of new antimicrobial strategies. Antimicrobial peptides (AMPs) are very promising molecules to fight microbial infection since they kill quickly bacteria and, in some cases, target bacterial membrane. Although some AMPs may be stable against proteolytic degradation by chemical modification, in general, low AMP activity and stability in the presence of serum and proteolytic enzymes as well as their cytotoxicity have impaired their clinical translation. Here, we describe a one-step methodology to generate AMP-conjugated gold nanoparticles (Au NPs), with a high concentration of AMPs (CM-SH) (≈240 AMPs per NP), controlled size (14 nm) and low polydispersity. AMP-conjugated Au NPs demonstrated higher antimicrobial activity and stability in serum and in the presence of non-physiological concentrations of proteolytic enzymes than soluble AMP, as well as low cytotoxicity against human cells. Moreover, the NPs demonstrated high antimicrobial activity after in vivo administration in a chronic wound and in an animal model of systemic infection.
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal; Biocant, Biotechnology Innovation Center, 3060-197, Cantanhede, Portugal.
authors: Akhilesh
authors: A
authors: Rai
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal; Biocant, Biotechnology Innovation Center, 3060-197, Cantanhede, Portugal.
authors: Sandra
authors: S
authors: Pinto
authors: Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
authors: Tiago R
authors: TR
authors: Velho
authors: CIEPQPF, Department of Chemical Engineering, University of Coimbra, 3030-790, Coimbra, Portugal.
authors: André F
authors: AF
authors: Ferreira
authors: Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
authors: Catarina
authors: C
authors: Moita
authors: Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
authors: Urvish
authors: U
authors: Trivedi
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal; Biocant, Biotechnology Innovation Center, 3060-197, Cantanhede, Portugal.
authors: Marta
authors: M
authors: Evangelista
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors: Michela
authors: M
authors: Comune
authors: Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
authors: Kendra P
authors: KP
authors: Rumbaugh
authors: CIEPQPF, Department of Chemical Engineering, University of Coimbra, 3030-790, Coimbra, Portugal.
authors: Pedro N
authors: PN
authors: Simões
authors: Instituto Gulbenkian de Ciência, 2780-156, Oeiras, Portugal.
authors: Luís
authors: L
authors: Moita
authors: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal; Biocant, Biotechnology Innovation Center, 3060-197, Cantanhede, Portugal. Electronic address: lino@biocant.pt.
authors: Lino
authors: L
authors: Ferreira
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D000072916:Peripheral Blood Stem Cells / Q000187:drug effects / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D006046:Gold
keywords: Antimicrobial activity; Antimicrobial peptide; Au NPs; Cecropin-melittin; One-step synthesis; Stability in protease and serum; Systemic infection