A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

Lenz, Anke Gabriele; Karg, Erwin; Lentner, Bernd; Dittrich, Vlad; Brandenberger, Christina; Rothen-Rutishauser, Barbara; Schulz, Holger; Ferron, George A; Schmid, Otmar (2009). A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles. Particle and fibre toxicology, 6, p. 32. London: BioMed Central 10.1186/1743-8977-6-32

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BACKGROUND: Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), in vitro cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface. RESULTS: A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (<12%), low-stress and efficient delivery of nanoparticles, or dissolved substances, to cells cultured at the air-liquid interface. Validation with various types of nanoparticles (Au, ZnO and carbon black nanoparticles) and solutes (such as NaCl) showed that the ALICE provided spatially uniform deposition (<1.6% variability) and had no adverse effect on the viability of a widely used alveolar human epithelial-like cell line (A549). The cell deposited dose can be controlled with a quartz crystal microbalance (QCM) over a dynamic range of at least 0.02-200 mug/cm(2). The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber. Dose-response measurements with ZnO nanoparticles (0.3-8.5 mug/cm(2)) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 mug/cm(2 )ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels. CONCLUSION: The ALICE is a useful tool for dose-controlled nanoparticle (or solute) exposure of cells at the air-liquid interface. Significant differences between cellular response after ZnO nanoparticle exposure under submerged and air-liquid interface conditions suggest that pharmaceutical and toxicological studies with inhaled (nano-)particles should be performed under the more realistic air-liquid interface, rather than submerged cell conditions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

UniBE Contributor:

Brandenberger, Christina and Rothen-Rutishauser, Barbara

ISSN:

1743-8977

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:11

Last Modified:

04 Jan 2015 02:05

Publisher DOI:

10.1186/1743-8977-6-32

PubMed ID:

20015351

Web of Science ID:

000273444200001

BORIS DOI:

10.7892/boris.31056

URI:

https://boris.unibe.ch/id/eprint/31056 (FactScience: 195455)

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