In vitro toxicity of nanoceria: effect of coating and stability in biofluids

Abstract

Due to the increasing use of nanometric cerium oxide in applications, concerns about the toxicity of these particles have been raised and have resulted in a large number of studies. We report here on the interactions between 7 nm anionically charged cerium oxide particles and living mammalian cells. By a modification of the particle coating including low-molecular weight ligands and polymers, two generic behaviours are compared: particles coated with citrate ions that precipitate in biofluids and particles coated with poly(acrylic acid) that are stable and remain nanometric. We find that nanoceria covered with both coating agents are taken up by mouse fibroblasts and localized into membrane-bound compartments. However, flow cytometry and electron microscopy reveal that as a result of their precipitation, citrate-coated particles interact more strongly with cells. At cerium concentration above 1 mM, only citrate-coated nanoceria (and not particles coated with poly(acrylic acid)) display toxicity and moderate genotoxicity. The results demonstrate that the control of the surface chemistry of the particles and its ability to prevent aggregation can affect the toxicity of nanomaterials.

Keywords::

• nanoparticles
• interfaces
• cells
• spectrometry
• toxicity

Acknowledgments

We thank Armelle Baeza-Squiban, Jean-Paul Chapel, Gaelle Charron, Emek Seyrek, Sonja Boland for fruitful discussions. We thank Frédéric Herbst from the Laboratoire Interdisciplinaire Carnot de Bourgogne for his help in the scanning electron microscopy studies and Virginie Garnier-Thibaud for the TEM measurements at the microscopic platform of the University Pierre et Marie Curie (Paris 6). ANR (Agence Nationale de la Recherche) and CGI (Commissariat à l’Investissement d’Avenir) are gratefully acknowledged for their financial support of this work through Labex SEAM (Science and Engineering for Advanced Materials and devices). This research was supported in part by the Agence Nationale de la Recherche under the contract ANR-09-NANO-P200-36.