Not ready to use – overcoming pitfalls when dispersing nanoparticles in physiological media

Abstract

Industrial nanoparticles are not developed to be compatible with in vitro cell culture assays which are carried out in isotonic solutions at physiological pH and often in the presence of proteins. The tendency of nanoparticles to deagglomerate or agglomerate is strongly sensitive to these parameters. The state of agglomeration and the protein corona bear an important influence on the level of toxic effects via the change of transport mechanisms and surface coating. Here we rigorously characterized the interaction of nanoparticles with physiological media for in vitro nanotoxicology experiments. Beyond adsorption of proteins on metal oxide and polymeric nanoparticles, we quantified nanoparticle deagglomeration due to adsorbing proteins acting as protection colloids. We report on previously neglected, but indispensable testing of sterility and measures to ensure it. Our findings result in a checklist of pre-requirements for dispersion of nanoparticles in physiological media and for reliable attribution of potential toxic effects.

• Nanoparticles
• sterility
• serum
• deagglomeration
• adsorption

Acknowledgements

For the characterization of the intrinsic nanoparticle properties, we thank Gerhard Cox (BASF: XRD, XPS) and Thomas Frechen (BASF: TEM). We acknowledge excellent laboratory support from Manfred Stadler (BASF). This project was partially supported by the Federal German Ministry of Education and Research BMBF (NanoCare; Förderkennzeichen 03X0021C).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.