Macrophage Polarization Status Impacts Nanoceria Cellular Distribution but Not Its Biotransformation or Ferritin Effects

Uschi M. Graham, Alan K. Dozier, David J. Feola, Michael T. Tseng, Robert A. Yokel

Research output: Contribution to journalArticlepeer-review


The innate immune system is the first line of defense against external threats through the initiation and regulation of inflammation. Macrophage differentiation into functional phenotypes influences the fate of nanomaterials taken up by these immune cells. High-resolution electron microscopy was used to investigate the uptake, distribution, and biotransformation of nanoceria in human and murine M1 and M2 macrophages in unprecedented detail. We found that M1 and M2 macrophages internalize nanoceria differently. M1-type macrophages predominantly sequester nanoceria near the plasma membrane, whereas nanoceria are more uniformly distributed throughout M2 macrophage cytoplasm. In contrast, both macrophage phenotypes show identical nanoceria biotransformation to cerium phosphate nanoneedles and simultaneous nanoceria with ferritin co-precipitation within the cells. Ferritin biomineralization is a direct response to nanoparticle uptake inside both macrophage phenotypes. We also found that the same ferritin biomineralization mechanism occurs after the uptake of Ce-ions into polarized macrophages and into unpolarized human monocytes and murine RAW 264.7 cells. These findings emphasize the need for evaluating ferritin biomineralization in studies that involve the internalization of nano objects, ranging from particles to viruses to biomolecules, to gain greater mechanistic insights into the overall immune responses to nano objects.

Original languageEnglish
Article number2298
Issue number16
StatePublished - Aug 2023

Bibliographical note

Funding Information:
This research was funded by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM109195.

Publisher Copyright:
© 2023 by the authors.


  • analytical microscopy
  • bioprocessing
  • cerium phosphate
  • iron biomineralization
  • macrophage phenotype
  • nanotoxicology

ASJC Scopus subject areas

  • Chemical Engineering (all)
  • Materials Science (all)


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