title: Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration.
abstract: Surface chemistry plays an important role in gold nanoparticles (AuNPs) stability and biocompatibility, which are crucial for their implementation into the clinical setting. We evaluated short- (30 min) and long-term (28 days) biodistribution and toxicity of ~20 nm citrate- and pentapeptide CALNN-coated AuNPs after a single intravenous injection in rats. The pattern of AuNPs distribution in Cit- and CALNN-AuNPs-injected rats was very similar in the assessed time-points. Both AuNPs were quickly removed from the bloodstream and preferentially accumulated in the liver. At 28 days liver remained the main accumulation site but at significantly lower levels compared to those found at 30 min. Spleen atrophy and hematological findings compatible with mild anemia were observed in CALNN-AuNPs-administered rats. Under our experimental conditions, surface coating had more impact on toxicity rather than on biodistribution of the AuNPs. Improvements in the design of capping peptides need to be done to increase biomedical applicability of peptide-coated AuNPs.
  
  
  BACKGROUND
  The biodistribution and toxicity of ~ 20 nm citrate- and pentapeptide CALNN-coated gold nanoparticles was investigated after a single intravenous injection in rats. Rapid clearance and hepatic accumulation was found at 30-minutes, whereas mild anemia and spleen atrophy was seen 28 days post injection. The authors also concluded that the toxicity was related to the capping proteins as opposed to the biodistribution of the particles, providing important suggestion for future design of gold nanoparticles.
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal. Electronic address: teixeirafraga@hotmail.com.
authors.forename: Sónia
authors.initials: S
authors.lastname: Fraga
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Brandão
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Soares
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Morais
authors.affiliation: CIAFEL, Faculty of Sports, University of Porto, Porto, Portugal.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Pereira
authors.affiliation: REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Soares
authors.affiliation: REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Neves
authors.affiliation: REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
authors.forename: Eulália
authors.initials: E
authors.lastname: Pereira
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Maria de Lourdes
authors.initials: Mde L
authors.lastname: Bastos
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal. Electronic address: helenacarmo@ff.up.pt.
authors.forename: Helena
authors.initials: H
authors.lastname: Carmo
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D006046:Gold / Q000737:chemistry*; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D053758:Nanoparticles / Q000378:metabolism*; D051381:Rats
chemical_list: D006046:Gold
keywords: Biodistribution; Gold nanoparticles; Intravenous administration; Rat; Toxicity