title: Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections.
abstract: Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using a zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections.
authors.affiliation: Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Díez-Martínez
authors.affiliation: Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: García-Fernández
authors.affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre, i+12, Pz/ Ramón y Cajal s/n, 28040, Madrid, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Manzano
authors.affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre, i+12, Pz/ Ramón y Cajal s/n, 28040, Madrid, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Martínez
authors.affiliation: Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Domenech
authors.affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre, i+12, Pz/ Ramón y Cajal s/n, 28040, Madrid, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vallet-Regí
authors.affiliation: Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: García
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001310:Auranofin / Q000008:administration & dosage* / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers; D065546:Drug Liberation; D019344:Lactic Acid / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D000900:Anti-Bacterial Agents; D018501:Antirheumatic Agents; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001310:Auranofin