Uptake and toxicity of cerium dioxide nanoparticles with different aspect ratio

Min Sung Kang, Gwang Hee Lee, Ik Hwan Kwon, Mi Jin Yang, Min Beom Heo, Jae Won Choi, Tae Geol Lee, Cheol Ho Yoon, Bosung Baek, Myeong Chang Sung, Dong Wan Kim, Eun Jung Park

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Cerium dioxide nanoparticles (CeONPs) have been extensively applied in research for future energy development due to two common oxidation states on their surface. Considering that shape (aspect ratio) is a key determinant of NPs-induced toxicity, we compared the toxicity of hexagonal (H)- and rod-shaped (R)-CeONPs in mice. At 24 h after pharyngeal aspiration, both types of CeONPs recruited surrounding immune cells (monocytes and neutrophils) into the lung, and R-CeONPs induced a more severe pulmonary inflammatory response compared with H-CeONPs. To identify an indicator to predict pulmonary inflammatory responses at the cellular level, we also investigated their responses in alveolar macrophage cells. At 24 h after treatment, both types of CeONPs were mainly located within the vacuoles (partially, in the lysosome) in the cytoplasm. Mitochondrial damage, intracellular calcium accumulation, and increased NO production were observed in cells exposed to both types of CeONPs, ultimately resulting in a decrease in cell viability. More interestingly, both types of CeONPs formed multinucleated giant cells. Meanwhile, contrary to when suspended in deionized water, R-CeONPs were strongly aggregated with a negative charge in cell culture media, whereas H-CeONPs were relatively well-dispersed with a positive charge. R-CeONPs-induced lysosomal extension was also recovered by premix with negatively charged DNA, and even NPs suspended in cell culture media without cells were detected under the FACS system, suggesting interference by protein corona. Therefore, we suggest that shape (aspect ratio) is an important factor determining inhaled NPs-induced pathology and that the effect of the surface charge and protein corona should be carefully considered in interpreting results derived from in vitro tests. Furthermore, we propose that the relationship between the formation of multinucleated giant cells and the inflammatory response of inhaled CeONPs should be further studied.

Original languageEnglish
Pages (from-to)196-209
Number of pages14
JournalToxicology Letters
Publication statusPublished - 2023 Jan 15

Bibliographical note

Funding Information:
This research was supported by a grant from the Ministry of Science and ICT ( 2021M3A7B6031389 and 2021R1F1A1054211 ).

Publisher Copyright:
© 2022 Elsevier B.V.


  • Alveolar macrophages
  • Cerium dioxide nanoparticles
  • Lung
  • Multinucleated giant cells
  • Protein corona

ASJC Scopus subject areas

  • Toxicology


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