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: 3.98). 09/2009; 242(1):56-65. DOI: 10.1016/j.taap.2009.09.014
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs.
    International Journal of Molecular Sciences 01/2014; 15(3):4795-822. · 2.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In healthy lungs, deposited micrometer-sized particles are efficiently phagocytosed by macrophages present on airway surfaces; however, uptake of nanoparticles (NP) by macrophages appears less effective and is largely unstudied in lung disease. Using mouse models of allergic asthma and chronic obstructive pulmonary disease (COPD), we investigated NP uptake after challenge with common biogenic ambient air microparticles.
    BMC Pulmonary Medicine 07/2014; 14(1):116. · 2.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gold nanoparticles (AuNP) provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of 198Au-radio-labelled monodisperse, well-characterized, negatively-charged AuNP of five different sizes (1.4, 2.8, 5, 18, 80, 200 nm) and 2.8 nm AuNP with positive surface charges. At 1-h, 3-h, and 24-h the biodistribution of the AuNP was quantitatively measured by gamma-spectrometry to be used for comprehensive risk assessment. Our study shows, as AuNP get smaller, they are more likely to cross the air-blood-barrier (ABB) depending strongly on the inverse diameter d-1of their gold core; i.e. their specific surface area (SSA). So, 1.4 nm AuNP (highest SSA) translocated most while 80 nm AuNP (lowest SSA) translocated least, but 200 nm particles did not follow the d-1 relation translocating significantly higher than 80 nm AuNP. However, relative to the AuNP which had crossed the ABB, their retention in most of the secondary organs and tissues was SSA-independent. Only renal filtration, retention in blood and excretion via urine further declined with d-1 of AuNP core. Translocation of 5, 18 and 80 nm AuNP is virtually complete after 1-h, while 1.4 nm AuNP continue to translocate until 3-h. Translocation of negatively charged 2.8 nm AuNP was significantly higher than for positively charged 2.8 nm AuNP. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge.
    ACS Nano 12/2013; · 12.03 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014

Similar Publications