Nanoceria distribution and effects are mouse-strain dependent

Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO2 nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. Electron microscopy showed intracellular nanoceria particles bioprocessed to form crystalline cerium phosphate nanoneedles. Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. Nanoceria uptake, initiation of bioprocessing, and crystalline cerium phosphate nanoneedle formation were rapid. Ferritin greatly increased with a macrophage phenotype-dependent distribution. Further study will be needed to understand the mechanisms underlying the observed differences.

Original languageEnglish
Pages (from-to)827-846
Number of pages20
Issue number6
StatePublished - Jul 2 2020

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [Grant no. R01GM109195]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Institute for Occupational Safety and Health. The authors gratefully acknowledge Marsha L. Ensor, Shekinah Alfaro, and Shristi Shrestha for their excellent contributions to this research.

Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.


  • BALB/c mice
  • C57BL/6 mice
  • caspase-1
  • ferritin
  • liver
  • nanoceria

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology


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