title: Bactericidal Effect of Gold-Chitosan Nanocomposites in Coculture Models of Pathogenic Bacteria and Human Macrophages.
abstract: The ability of pathogenic bacteria to develop resistance mechanisms to avoid the antimicrobial potential of antibiotics has become an increasing problem for the healthcare system. The search for more effective and selective antimicrobial materials, though not harmful to mammalian cells, seems imperative. Herein we propose the use of gold-chitosan nanocomposites as effective bactericidal materials avoiding damage to human cells. Nanocomposites were obtained by taking advantage of the reductive and stabilizing action of chitosan solutions on two different gold precursor concentrations. The resulting nanocomposites were added at different final concentrations to a coculture model formed by Gram-positive (Staphylococcus aureus) or Gram-negative (Escherichia coli) bacteria and human macrophages. Gold-chitosan colloids exhibited superior bactericidal ability against both bacterial models without showing cytotoxicity on human cells at the concentrations tested. Morphological and in vitro viability studies supported the feasibility of the infection model here described to test novel bactericidal nanomaterials. Flow cytometry and scanning electron microscopy analyses pointed to the disruption of the bacterial wall as the lethal mechanism. Data obtained in the present study suggest that gold-chitosan nanocomposites are powerful and promising nanomaterials for reducing bacteria-associated infections, respecting the integrity of mammalian cells, and displaying high selectivity against the studied bacteria.
authors.affiliation: Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza , Campus Rı́o Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain.|Aragon Health Research Institute (IIS Aragón) , 50009 Zaragoza, Spain.
authors.forename: Gracia
authors.identifier: http://orcid.org/0000-0003-2293-363X
authors.initials: G
authors.lastname: Mendoza
authors.affiliation: Faculty of Chemistry, Jagiellonian University , Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Regiel-Futyra
authors.affiliation: Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza , Campus Rı́o Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain.|Aragon Health Research Institute (IIS Aragón) , 50009 Zaragoza, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Andreu
authors.affiliation: Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza , Campus Rı́o Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN , 28029 Madrid, Spain.|Aragon Health Research Institute (IIS Aragón) , 50009 Zaragoza, Spain.
authors.forename: Víctor
authors.identifier: http://orcid.org/0000-0002-6873-5244
authors.initials: V
authors.lastname: Sebastián
authors.affiliation: Faculty of Chemistry, Jagiellonian University , Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kyzioł
authors.affiliation: Faculty of Chemistry, Jagiellonian University , Ingardena 3, 30-060 Kraków, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Stochel
authors.affiliation: Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza , Campus Rı́o Ebro-Edificio I+D, C/Mariano Esquillor S/N, 50018 Zaragoza, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN , 28029 Madrid, Spain.|Aragon Health Research Institute (IIS Aragón) , 50009 Zaragoza, Spain.
authors.forename: Manuel
authors.identifier: http://orcid.org/0000-0003-3165-0156
authors.initials: M
authors.lastname: Arruebo
mesh_terms: D000900:Anti-Bacterial Agents; D001419:Bacteria; D048271:Chitosan; D018920:Coculture Techniques; D006046:Gold; D006801:Humans; D008264:Macrophages; D053768:Metal Nanoparticles; D053761:Nanocomposites
chemical_list: D000900:Anti-Bacterial Agents; D006046:Gold; D048271:Chitosan
keywords: bactericidal nanomaterials; chitosan; gold nanoparticles; infection; nanocomposites