title: Influence of the surface coating on the cytotoxicity, genotoxicity and uptake of gold nanoparticles in human HepG2 cells.
abstract: The toxicological profile of gold nanoparticles (AuNPs) remains controversial. Significant efforts to develop surface coatings to improve biocompatibility have been carried out. In vivo biodistribution studies have shown that the liver is a target for AuNPs accumulation. Therefore, we investigated the effects induced by ~20 nm spherical AuNPs (0-200 μM Au) with two surface coatings, citrate (Cit) compared with 11-mercaptoundecanoic acid (11-MUA), in human liver HepG2 cells. Cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release assays after 24 to 72 h of incubation. DNA damage was assessed by the comet assay, 24 h after incubation with the capped AuNPs. Uptake and subcellular distribution of the tested AuNPs was evaluated by quantifying the gold intracellular content by graphite furnace atomic absorption spectrometry (GFAAS) and transmission electron microscopy (TEM), respectively. The obtained results indicate that both differently coated AuNPs did not induce significant cytotoxicity. An inverse concentration-dependent increase in comet tail intensity and tail moment was observed in Cit-AuNPs- but not in MUA-AuNPs-exposed cells. Both AuNPs were internalized in a concentration-dependent manner. However, no differences were found in the extent of the internalization between the two types of NPs. Electron-dense deposits of agglomerates of Cit- and MUA-AuNPs were observed either inside endosomes or in the intercellular spaces. In spite of the absence of cytotoxicity, DNA damage was observed after exposure to the lower concentrations of Cit- but not to MUA-AuNPs. Thus, our data supports the importance of the surface properties to increase the biocompatibility and safety of AuNPs.
authors.affiliation: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal. teixeirafraga@hotmail.com
authors.forename: Sónia
authors.initials: S
authors.lastname: Fraga
authors.forename: Helena
authors.initials: H
authors.lastname: Faria
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Soares
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.forename: Leonor
authors.initials: L
authors.lastname: Soares
authors.forename: Eulália
authors.initials: E
authors.lastname: Pereira
authors.forename: Cristiana
authors.initials: C
authors.lastname: Costa-Pereira
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Teixeira
authors.forename: Maria
authors.initials: M
authors.lastname: de Lourdes Bastos
authors.forename: Helena
authors.initials: H
authors.lastname: Carmo
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D019343:Citric Acid / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D005227:Fatty Acids / Q000737:chemistry; D042822:Genomic Instability; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: C505222:11-mercaptoundecanoic acid; D020099:Coated Materials, Biocompatible; D005227:Fatty Acids; D013438:Sulfhydryl Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D019343:Citric Acid; D006046:Gold; C022616:thiazolyl blue
keywords: DNA damage; HepG2 cells; cellular uptake; cytotoxicity; gold nanoparticles; surface properties