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Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model

Institute of Anatomy, Division of Histology, University of Bern, Bern, Switzerland.
Toxicology and Applied Pharmacology (Impact Factor: 3.63). 09/2009; 242(1):56-65. DOI: 10.1016/j.taap.2009.09.014
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ABSTRACT The impact of nanoparticles (NPs) in medicine and biology has increased rapidly in recent years. Gold NPs have advantageous properties such as chemical stability, high electron density and affinity to biomolecules, making them very promising candidates as drug carriers and diagnostic tools. However, diverse studies on the toxicity of gold NPs have reported contradictory results. To address this issue, a triple cell co-culture model simulating the alveolar lung epithelium was used and exposed at the air-liquid interface. The cell cultures were exposed to characterized aerosols with 15 nm gold particles (61 ng Au/cm2 and 561 ng Au/cm2 deposition) and incubated for 4 h and 24 h. Experiments were repeated six times. The mRNA induction of pro-inflammatory (TNFalpha, IL-8, iNOS) and oxidative stress markers (HO-1, SOD2) was measured, as well as protein induction of pro- and anti-inflammatory cytokines (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, TNFalpha, INFgamma). A pre-stimulation with lipopolysaccharide (LPS) was performed to further study the effects of particles under inflammatory conditions. Particle deposition and particle uptake by cells were analyzed by transmission electron microscopy and design-based stereology. A homogeneous deposition was revealed, and particles were found to enter all cell types. No mRNA induction due to particles was observed for all markers. The cell culture system was sensitive to LPS but gold particles did not cause any synergistic or suppressive effects. With this experimental setup, reflecting the physiological conditions more precisely, no adverse effects from gold NPs were observed. However, chronic studies under in vivo conditions are needed to entirely exclude adverse effects.

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Available from: Christina Brandenberger, Jul 29, 2015
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    • "In general, most studies have excluded the toxicity of gold nanoparticles (4–18 nm in diameter) (Connor et al., 2005; Khan et al., 2007; Shukla et al., 2005) studying cell viability, pro-apoptotic effects, oxidative stress and inflammatory response. Brandenberger et al. (2010) concluded that non functionalized gold particles with a size of 13–20 nm in diameter do not cause acute adverse effects. In contrast, cytotoxic and pro-apoptotic effects of gold particles 62 nm have been reported (Pan et al., 2007; Tsoli et al., 2005), as well as the impact of the charge of surface coatings on 2 nm particles on * Corresponding author. "
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    • "After the triple cell coculture was established, cell densities of macrophages and dendritic cells within the culture were quantified using the specific surface markers CD14 and CD86 for the labeling of macrophages and dendritic cells, respectively, and the quantitative occurrence of macrophages and dendritic cells resembled very closely the in-vivo situation (Blank et al., 2007). After its thorough evaluation, this model was exposed to particles (either airborne or suspended in medium) of different materials (polystyrene, titanium dioxide and gold) and of different sizes ( r1 mm) (Blank et al., 2007; Rothen- Rutishauser, 2007; Rothen-Rutishauser et al., 2008b; Brandenberger et al., 2010). Translocation and cellular localization of particles were studied as well as the effects of particles on cellular interplay and signaling. "
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