Original Article
Gold nanoparticles: Distribution, bioaccumulation and toxicity. In vitro and in vivo studies

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Abstract

Concerns about the bioaccumulation and toxicity of gold nanoparticles inside humans have recently risen. HT-29 and HepG2 cell lines and Wistar rats were exposed to 10, 30 or 60 nm gold nanoparticles to determine their tissue distribution, subcellular location and deleterious effects. Cell viability, ROS production and DNA damage were evaluated in vitro. Lipid peroxidation and protein carbonylation were determined in liver. ICP-MS measurements showed the presence of gold in intestine, kidney, liver, spleen, feces and urine. Subcellular locations of gold nanoparticles were observed in colon cells and liver samples by transmission electron microscopy. Inflammatory markers in liver and biochemical parameters in plasma were measured to assess the inflammatory status and presence of tissue damage. The size of the nanoparticles determined differences in the biodistribution and the excretion route. The smallest nanoparticles showed more deleterious effects, confirmed by their location inside the cell nucleus and the higher DNA damage.

Graphical Abstract

10, 30 and 60 nm diameter gold nanoparticles were administered to cell cultures and Wistar rats. Size-dependent biodistribution and excretion routes were observed in vivo. The accumulation of gold in the organs and the subcellular distribution caused an overproduction of free radicals and reactive oxygen species that originated protein carbonylation, lipid peroxidation and DNA damage. The smallest nanoparticles showed the most deleterious effects.

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Section snippets

Gold nanoparticles

Citrate-stabilized gold nanoparticles with 10, 30 or 60 nm of diameter size, suspended in ultrapure water at 50 mg/L, were purchased at the National Institute of Standard and Technology (NIST RM 8011, 8012 and 8013, Gaithersburg, USA). The reference values obtained by TEM were 8.9 ± 0.1, 27.6 ± 2.1, and 56.0 ± 0.5 nm respectively. In order to confirm the presence of monodisperse Au nanoparticles, the purchased materials were regularly checked in our laboratory. The lowest dose of AuNPs used in the

Cell viability assay

Figure 1 shows lactate dehydrogenase assay in HepG2 cells. The AuNPs provoked a decrease in viability at 16 h, compared to the control group. This viability tended to normalize after 32 h. No significant differences were found regarding the size of the nanoparticles.

ROS production

The effect of AuNPs on the generation of ROS was confirmed after observing an increase in every sample treated with 10 ppm AuNPs at 16 h, as shown in Figure 2. This overproduction was normalized after 32 h of treatment. As expected,

Discussion

Gold nanoparticles have been found to be useful in a wide range of applications, like the delivery and controlled release of a variety of chemical agents including anticancer drugs, antibiotics, amino acids, peptides, glucose, antioxidants, nucleic acids, and isotopes.13 However, the increase in their use has raised concerns about the possible interactions in vivo and the unexpected responses inside humans and other living organisms.31 Thus, the aim of this study was to determine the tissue

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    This work was supported by the Spanish Ministry for Science and Innovation (Grant Number CTQ2011-23038) and the Spanish Ministry for Education, Culture and Sports (Grant Number FPU13/00062). These results are included in the PhD thesis of Carlos López Chaves from the University of Granada, Nutrition and Food Sciences doctoral program.

    The authors have no conflicts of interest to declare.

    1

    These authors contributed equally in this work.

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