Advanced in vitro exposure systems.

Distribution of polymer-coated gold nanoparticles in a 3D lung model and indication of apoptosis after repeated exposure

6. Jun. 2018

DOI: 10.2217/nnm-2017-0358

Savvina Chortarea1,2, Kleanthis Fytianos1,3,4, Laura Rodriguez-Lorenzo1, Alke Petri-Fink1,5 & Barbara Rothen-Rutishauser1
1BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
2Laboratory for Particles – Biology Interactions, Empa, Swiss Federal Laboratories for Materials, Science & Technology, St Gallen, Switzerland
3Department of Pulmonary Medicine, University of Bern, Bern, Switzerland
4Department of Clinical Research, University of Bern, Bern, Switzerland
5Department of Chemistry, University of Fribourg, Fribourg, Switzerland

The distribution and impact of aerosol-delivered functionalized AuNPs upon repeated administration were explored in a complex in vitro human lung epithelial tissue barrier model applying an air–liquid interface exposure approach. Nanoparticles were aerosolized using the Air-Liquid Interface system consisting of a nebulizer, an exposure and an incubation chamber connected to an air-flow system to provide optimum conditions for cell cultivation as well as a quartz crystal microbalance for online measurements of the NP dose deposited on the cells surface.

 

Aim

The distribution and impact of aerosol-delivered gold nanoparticles (AuNPs) functionalized with a mixture of aminated-polyvinyl alcohol and amino-PEG ([polyvinyl alcohol/PEG]-NH2) upon repeated administration onto a 3D lung model were explored. 
Materials & methods: AuNPs were aerosolized and uptake and epithelial translocation was assessed by inductively coupled plasma optical-emission spectroscopy, flow cytometry and electron microscopy. In addition, cytotoxicity, apoptosis and proinflammation were evaluated. 
Results: Repeated AuNP aerosolization resulted in NP accumulation in macrophages and epithelial cells. Dendritic cells demonstrated substantial NP internalization after single administration which was reduced in later time points. No cytotoxicity or proinflammation was observed but after 96 h significant apoptosis was induced by the polymer coating. 
Conclusion: These results indicate the importance of repeated exposures in addressing potential effects of NPs.

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