A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials

Abstract

A novel method is presented which is suitable for assessing in vivo the link between the physicochemical properties of engineered nanomaterials (ENM) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe₂O₃, SiO₂, Ag and Ag/SiO₂ was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe₂O₃ can cause both pulmonary and cardiovascular effects.

Keywords::

• Engineered nanomaterials
• in vivo inhalation
• nanotoxicology
• cardiovascular and pulmonary effects
• nanotoxicology
• iron oxide

Acknowledgements

This research project was supported by NIEHS Grant (ES-0000002), the Swiss National Science Foundation (Grant 200020-126694) and the European Research Council. The authors also thank Dr Frank Krumeich (Electron Microscopy Center, ETH Zurich) for the electron microscopy analysis.