Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies

Abstract

A novel system for generation of engineered nanomaterials (ENMs) suitable for in situ toxicological characterization within biological matrices was developed. This Versatile Engineered Nanomaterial Generation System (VENGES) is based on industry-relevant, flame spray pyrolysis aerosol reactors that can scaleably produce ENMs with controlled primary and aggregate particle size, crystallinity, and morphology. ENMs are produced continuously in the gas phase, allowing their continuous transfer to inhalation chambers, without altering their state of agglomeration. Freshly generated ENMs are also collected on Teflon filters for subsequent physicochemical and morphological characterization and for in vitro toxicological studies. The ability of the VENGES system to generate families of ENMs of pure and selected mixtures of iron oxide, silica, and nanosilver with controlled physicochemical properties was demonstrated using a range of state-of-the-art-techniques. Specific surface area was measured by nitrogen adsorption using the Brunauer–Emmett–Teller method, and crystallinity was characterized by X-ray diffraction. Particle morphology and size were evaluated by scanning and transmission electron microscopy. The suitability of the VENGES system for toxicological studies was also shown in both in vivo and in vitro studies involving Sprague–Dawley rats and human alveolar-like monocyte derived macrophages, respectively. We demonstrated linkage between physicochemical ENM properties and potential toxicity.

Keywords::

• Engineered nanomaterials
• in vivo inhalation studies
• in vitro toxicological studies
• iron oxide
• silica
• nanosilver

Acknowledgments

The authors thank Dr. David Bell from the Harvard Center for Nanoscale Systems for the STEM analysis, as well as Dr. Frank Krumeich (ETH) and the Electron Microscopy Center of ETH Zurich (EMEZ) for providing the necessary infrastructure for the TEM images. We thank Thomas Donaghey for technical support with the in vivo toxicology studies and Melissa Curran for helpful editorial suggestions and TETHIS for providing the FSP apparatus for the ENM synthesis.

Declaration of interest

This work was supported financially by the Harvard University, the HSPH-NIEHS Center (grant #ES000002), and ETH Zürich (ETH Research grant TH-09 06-2). The authors report no conflicts of interest.