title: High Antimicrobial Activity and Low Human Cell Cytotoxicity of Core-Shell Magnetic Nanoparticles Functionalized with an Antimicrobial Peptide.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory concentration (MIC) of the AMP-NP for Escherichia coli was 0.4 μg/mL, 10-times lower than the MIC of soluble CM. The antimicrobial activity of CM depends on the length of the spacer between the CM and the NP. AMP-NPs are taken up by endothelial (between 60 and 170 pg of NPs per cell) and macrophage (between 18 and 36 pg of NPs per cell) cells and accumulate preferentially in endolysosomes. These NPs have no significant cytotoxic and pro-inflammatory activities for concentrations up to 200 μg/mL (at least 100 times higher than the MIC of soluble CM). Our results in membrane models suggest that the selectivity of AMP-NPs for bacteria and not eukaryotic membranes is due to their membrane compositions. The AMP-NPs developed here open new opportunities for infection-site targeting.
authors.affiliation: CIEPQPF, Department of Chemical Engineering, University of Coimbra , 3030-790 Coimbra, Portugal.
authors.forename: Hajar
authors.initials: H
authors.lastname: Maleki
authors.affiliation: Biocant-Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal.|CNC-Center of Neurosciences and Cell Biology, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Rai
authors.affiliation: Biocant-Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal.|CNC-Center of Neurosciences and Cell Biology, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Biocant-Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal.|CNC-Center of Neurosciences and Cell Biology, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Evangelista
authors.affiliation: Biocant-Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal.|CNC-Center of Neurosciences and Cell Biology, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: Renato M S
authors.initials: RM
authors.lastname: Cardoso
authors.affiliation: Biocant-Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal.|CNC-Center of Neurosciences and Cell Biology, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Paulo
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of Blood and Transplantation , 3041-861 Coimbra, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Carvalheiro
authors.affiliation: Blood and Transplantation Center of Coimbra, Portuguese Institute of Blood and Transplantation , 3041-861 Coimbra, Portugal.
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
authors.affiliation: Novel Drug Delivery Systems Department, Iran Polymer and Petrochemical Institute , 13115-14977 Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Imani
authors.affiliation: Department of Material Science and Engineering, Sharif University of Technology , 11365-11155 Tehran, Iran.|Institute for Nanoscience and Nanotechnology, Sharif University of Technology , 11365-11155 Tehran, Iran.
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Simchi
authors.affiliation: CIEPQPF, Department of Chemical Engineering, University of Coimbra , 3030-790 Coimbra, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Durães
authors.affiliation: CIEPQPF, Department of Chemical Engineering, University of Coimbra , 3030-790 Coimbra, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Portugal
authors.affiliation: Biocant-Biotechnology Innovation Center, 3060-197 Cantanhede, Portugal.|CNC-Center of Neurosciences and Cell Biology, University of Coimbra , 3004-517 Coimbra, Portugal.
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents; D006046:Gold; D006801:Humans; D008280:Magnetics; D058185:Magnetite Nanoparticles; D053758:Nanoparticles; D010455:Peptides
chemical_list: D000890:Anti-Infective Agents; D058185:Magnetite Nanoparticles; D010455:Peptides; D006046:Gold
keywords: antimicrobial peptide; cecropin melittin; core−shell nanoparticles; human cell biocompatibility; magnetic nanoparticles