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Gold nanoparticle aerosols for rodent inhalation and translocation studies

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Abstract

The intensive use of nano-sized particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of nanoparticles (NP) with biological systems after various routes of exposure needs to be investigated using well-characterized NP. We report here on the generation of gold-NP (Au-NP) aerosols for inhalation studies with the spark ignition technique, and their characterization in terms of chemical composition, physical structure, morphology, and specific surface area, and on interaction with lung tissues and lung cells after 1 h inhalation by mice. The originally generated agglomerated Au-NP were converted into compact spherical Au-NP by thermal annealing at 600 °C, providing particles of similar mass, but different size and specific surface area. Since there are currently no translocation data available on inhaled Au-NP in the 10–50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation in rodents. For anticipated in vivo systemic translocation and dosimetry analyses, radiolabeled Au-NP were created by proton irradiating the gold electrodes of the spark generator, thus forming gamma ray emitting 195Au with 186 days half-life, allowing long-term biokinetic studies. The dissolution rate of 195Au from the NP was below detection limits. The highly concentrated, polydisperse Au-NP aerosol (1–2 × 107 NP/cm3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation and number concentration. After collection on filters particles can be re-suspended and used for instillation or ingestion studies.

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Acknowledgments

This work was partially funded by HMGU: EU FP7 Projects NeuroNano, NMP4-SL-2008-214547; ENPRA, NMP4-SL-2009-228789; InLiveTox, NMP4-SL-2009-228625; UBern: Swiss National Science Foundation Project 310030-120763; UBremen: S.P. and L.M. would like to thank National Science Foundation and the Environmental Protection Agency under Cooperative Agreement Number DBI-0830117 for supporting this work. Key support was also provided by the US Public Health Service Grants U19 ES019528 (UCLA Center for NanoBiology and Predictive Toxicology), RO1 ES016746, and RC2 ES018766. S.P. and L.M. would also like to thank Prof. A. Rosenauer and M. Schowalter, Department of Physics, University of Bremen, for TEM and EDX analysis.

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Authors and Affiliations

  1. Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease (iLBD), Helmholtz Zentrum München—German Research Center for Environmental Health, Ingolstaedter Landstr. 1, 85764, Neuherberg, Munich, Germany

    Winfried Möller, Alexander Wenk, Shinji Takenaka, Otmar Schmid & Wolfgang G. Kreyling

  2. Institute for Health and Consumer Protection, Joint Research Centre of the European Commission, Via E. Fermi 2749, 21027, Ispra, VA, Italy

    Neil Gibson, Antonio Bulgheroni, Federica Simonelli, Jan Kozempel & Uwe Holzwarth

  3. Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3000, Bern 9, Switzerland

    Marianne Geiser, Christoph Wigge & Sylvie Eigeldinger-Berthou

  4. Department of Production Engineering, Foundation Institute of Materials Science (IWT), University of Bremen, Bremen, Germany

    Suman Pokhrel & Lutz Mädler

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  1. Winfried Möller
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  2. Neil Gibson
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  15. Wolfgang G. Kreyling
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Correspondence to Winfried Möller.

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Möller, W., Gibson, N., Geiser, M. et al. Gold nanoparticle aerosols for rodent inhalation and translocation studies. J Nanopart Res 15, 1574 (2013). https://doi.org/10.1007/s11051-013-1574-9

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