Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface

Particle and Fibre Toxicology, Nov 2017

The lung represents the primary entry route for airborne particles into the human body. Most studies addressed possible adverse effects using single (nano)particles, but aerosolic nanoparticles (NPs) tend to aggregate and form structures of several hundreds nm in diameter, changing the physico-chemical properties and interaction with cells. Our aim was to investigate how aggregation might affect the biodistribution; cellular uptake and translocation over time of aerosolized NPs at the air-blood barrier interface using a multicellular lung system. Model gold nanoparticles (AuNPs) were engineered and well characterized to compare single NPs with aggregated NPs with hydrodynamic diameter of 32 and 106 nm, respectively. Exposures were performed by aerosolization of the particles onto the air-liquid interface of a three dimensional (3D) lung model. Particle deposition, cellular uptake and translocation kinetics of single and aggregated AuNPs were determined for various concentrations, (30, 60, 150 and 300 ng/cm2) and time points (4, 24 and 48 h) using transmission electron microscopy and inductively coupled plasma optical emission spectroscopy. No apparent harmful effect for single and aggregated AuNPs was observed by lactate dehydrogenase assay, nor pro-inflammation response by tumor necrosis factor α assessment. The cell layer integrity was also not impaired. The bio-distribution revealed that majority of the AuNPs, single or aggregated, were inside the cells, and only a minor fraction, less than 5%, was found on the basolateral side. No significant difference was observed in the translocation rate. However, aggregated AuNPs showed a significantly faster cellular uptake than single AuNPs at the first time point, i.e. 4 h. Our studies revealed that aggregated AuNPs showed significantly faster cellular uptake than single AuNPs at the first time point, i.e. 4 h, but the uptake rate was similar at later time points. In addition, aggregation did not affect translocation rate across the lung barrier model since similar translocation rates were observed for single as well as aggregated AuNPs.

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Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface

Durantie et al. Particle and Fibre Toxicology Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface Estelle Durantie 0 2 Dimitri Vanhecke 0 2 Laura Rodriguez-Lorenzo 0 2 Flavien Delhaes 0 2 Sandor Balog 0 2 Dedy Septiadi 0 2 Joel Bourquin 0 2 Alke Petri-Fink 0 1 2 Barbara Rothen-Rutishauser 0 2 0 BioNanomaterials Group, Adolphe Merkle Institute, Université de Fribourg , Chemin des Verdiers 4, 1700 Fribourg , Switzerland 1 Chemistry Department, University of Fribourg , Chemin du Musée 9, 1700 Fribourg , Switzerland 2 BioNanomaterials Group, Adolphe Merkle Institute, Université de Fribourg , Chemin des Verdiers 4, 1700 Fribourg , Switzerland Background: The lung represents the primary entry route for airborne particles into the human body. Most studies addressed possible adverse effects using single (nano)particles, but aerosolic nanoparticles (NPs) tend to aggregate and form structures of several hundreds nm in diameter, changing the physico-chemical properties and interaction with cells. Our aim was to investigate how aggregation might affect the biodistribution; cellular uptake and translocation over time of aerosolized NPs at the air-blood barrier interface using a multicellular lung system. Results: Model gold nanoparticles (AuNPs) were engineered and well characterized to compare single NPs with aggregated NPs with hydrodynamic diameter of 32 and 106 nm, respectively. Exposures were performed by aerosolization of the particles onto the air-liquid interface of a three dimensional (3D) lung model. Particle deposition, cellular uptake and translocation kinetics of single and aggregated AuNPs were determined for various concentrations, (30, 60, 150 and 300 ng/cm2) and time points (4, 24 and 48 h) using transmission electron microscopy and inductively coupled plasma optical emission spectroscopy. No apparent harmful effect for single and aggregated AuNPs was observed by lactate dehydrogenase assay, nor pro-inflammation response by tumor necrosis factor α assessment. The cell layer integrity was also not impaired. The bio-distribution revealed that majority of the AuNPs, single or aggregated, were inside the cells, and only a minor fraction, less than 5%, was found on the basolateral side. No significant difference was observed in the translocation rate. However, aggregated AuNPs showed a significantly faster cellular uptake than single AuNPs at the first time point, i.e. 4 h. Conclusions: Our studies revealed that aggregated AuNPs showed significantly faster cellular uptake than single AuNPs at the first time point, i.e. 4 h, but the uptake rate was similar at later time points. In addition, aggregation did not affect translocation rate across the lung barrier model since similar translocation rates were observed for single as well as aggregated AuNPs. Aggregate; Gold nanoparticle; Air liquid interface cell exposure; Biodistribution; Human epithelial airway model; Translocation; Cellular uptake Background Agglomeration and/or aggregation is an ubiquitous phenomenon observed for nanoparticles (NPs), however, the interaction of NP agglomerates with cells/tissues have only rarely being studied, consequently very little is known on their interaction with biological systems and subsequent fate [ 1–3 ]. Agglomerates and aggregates are secondary entities in which single NPs, or primary particles, are held together. In agglomerates, primary particles are assembled by weak physical interactions (i.e. van der Waals forces) and the whole process is reversible, while aggregates are defined as comprising strongly bonded primary particles, and the process is irreversible [ 4 ]. Agglomerates and aggregates will be simplified to the aggregates term from now on. These assembled NPs systems display more complex physicochemical properties than single NPs as their size, morphology, surface area and effective density will depend additionally on the fractal dimension and packing factors [ 5–7 ]. Combustion-derived NPs, are major contributors of aggregates in the airborne ambient air and, have been associated to adverse health effect [ 8, 9 ]. During the combustion process, i.e. diesel or gasoline engines, unburned or partially burned fuel undergo nucleation process forming single particles with diameter of about 10–30 nm [ 10, 11 ]. These single particles can further collapse to form aggregates with mean diameter below 100 nm up to several hundreds of nm which results in a reduced concentration number [ 6, 12, 13 ]. Humans are constantly exposed to airborne particles of different sources in the environment which enter the human body mainly by inhalation. NPs with a diameter from 5 to 500 nm can enter and penetrate into the alveolar region of the lung by diffusion processed [ 14 ] and the deposited NPs have been shown to translocate across the air-blood barrier reaching the blood or lymphatic circulation, to be further dis (...truncated)


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Estelle Durantie, Dimitri Vanhecke, Laura Rodriguez-Lorenzo, Flavien Delhaes, Sandor Balog, Dedy Septiadi, Joel Bourquin, Alke Petri-Fink, Barbara Rothen-Rutishauser. Biodistribution of single and aggregated gold nanoparticles exposed to the human lung epithelial tissue barrier at the air-liquid interface, Particle and Fibre Toxicology, pp. 49,