Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Salik Hussain^1,*, Faris Al-Nsour^1,*, Annette B Rice¹, Jamie Marshburn¹, Zhaoxia Ji², Jeffery I Zink², Brenda Yingling¹, Nigel J Walker³, Stavros Garantziotis<sup>1

1</sup>Clinical Research Unit, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, ²UC Center for Environmental Implications of Nanotechnology University of California, Los Angeles, CA, ³Division of National Toxicology Program, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, USA

*Both are principal authors

Background: Cerium dioxide (CeO₂) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO₂ nanoparticles. We investigated the inflammation-modulating effects of CeO₂ nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes.
Methods: CD14⁺ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 µg/mL of CeO₂ nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10.
Results: CeO₂ nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (-14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14⁺ cells exposed to CeO₂ nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO₂ nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO₂ nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO₂ nanoparticles followed by lipopolysaccharide exposure.
Conclusion: CeO₂ nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.

Keywords: cerium dioxide, nanoparticle, nanomedicine, inflammation, human monocyte, lipopolysaccharides