In vivo toxicological evaluation of polymer brush engineered nanoceria: impact of brush charge

Abstract

Nanoceria has a broad variety of industrial and pharmacological applications due to its antioxidant activity. Nanoceria can be modified by surface coating with polyelectrolyte brushes. Brushes can increase the surface charge of nanoceria, providing greater aqueous stability while reducing agglomeration. However, surface-coating also behaves as a barrier around nanoceria, affecting its redox equilibrium and, hence, its biological and toxicological properties. In the present study, we examined whether bare nanoceria (CeO₂; 80–150 nm) and nanoceria modified by surface polymer brush, using negatively charged polyacrylic acid (CeO₂@PAA) and positively charged poly (2-(methacryloyloxy)ethyl-trimethyl-ammonium chloride (CeO₂@PMETAC), could induce systemic toxicity. As CeO₂ has limited colloidal stability, which might result in vascular occlusion, intraperitoneal injection was used instead of intravenous administration. C57Bl/6 mice were four times injected with three different doses of each nanoceria-based sample (corresponding to 1.8, 5.3 and 16 mg Ce/kg BW/administration) for a total period of 14 days. CeO₂@PMETAC induced a significant dose-dependent neutrophilia. Histopathological evaluation showed inflammatory processes in the capsule of liver, kidney, and spleen of animals at all doses of CeO₂@PMETAC, and with the highest dose of CeO₂@PAA and CeO₂. However, none of the nanoceria-based samples tested increased the level of DNA damage or micronuclei in blood cells, even though Ce was detected by inductively coupled plasma mass spectrometry analyses in the bone marrow. Only CeO₂@PMETAC induced the presence of megakaryocytes in the spleen. A higher accumulation of Ce in mononuclear phagocyte system organs (liver, spleen and bone marrow) was observed after CeO₂@PMETAC treatment compared with CeO₂@PAA and CeO₂.

Keywords:

• Cerium oxide nanoparticle
• polymer brush
• surface-coating
• in vivo toxicity
• genotoxicity

Acknowledgments

Mr. Djalma Santos, Ms. Debora Silva Santos, Ms. Nayara Miranda de Souza (University of Brasilia), and Mr. Javier Calvo (CIC biomaGUNE) are acknowledged for their excellent technical support. We would also like to thank Dr. Joan Cabellos and Dr. Gemma Janer (LEITAT, Spain) for their useful comments on the ICP-MS analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was funded by the European Commission project FP7 People-Pirses-BRASINOEU, Grant agreement 319816, and the Conselho Nacional de Pesquisa – Brasil - National of Science and Technology in Nanobiotechnology (INCT in Nanobiotechnology) Grant agreement 573880/2008-5.