Interactions of engineered nanomaterials in physiological media and implications for in vitro dosimetry

Abstract

In vitro toxicity assays are efficient and inexpensive tools for screening the increasing number of engineered nanomaterials (ENMs) entering the consumer market. However, the data produced by in vitro studies often vary substantially among different studies and from in vivo data. In part, these discrepancies may be attributable to lack of standardisation in dispersion protocols and inadequate characterisation of particle–media interactions which may affect the particle kinetics and the dose delivered to cells. In this study, a novel approach for preparation of monodisperse, stabilised liquid suspensions is presented and coupled with a numerical model which estimates delivered dose values. Empirically derived material- and media-specific functions are presented for each media–ENM system that can be used to convert administered doses to delivered doses. The interactions of ENMs with a variety of physiologic media were investigated and the importance of this approach was demonstrated by in vitro cytotoxicity assays using THP-1 macrophages.

Keywords::

• Nanotoxicology
• liquid suspension
• DLS
• dosimetry

Acknowledgements

The authors thank Dr. Georgios A. Sotiriou (Particle Technology Laboratory, ETH Zurich) for the electron microscopy imaging, BET and XRD analysis of the ENM samples, and Dr Justin G. Teeguarden (Pacific Northwest National Laboratory, Richland, WA, USA) for the providing the MATLAB software implementation of the ISDD dose delivery model.

Declarations of interest

The authors declared no personal interests related to this study. This research project was supported by NIEHS grant (ES-0000002) and the Center for Nanotechnology and Nanotoxicology at The Harvard School of Public Health.