Dependence of the Ce(iii)/Ce(iv) ratio on intracellular localization in ceria nanoparticles internalized by human cells

Daniela Ferraro, Ilenia G. Tredici, Paolo Ghigna, Hiram Castillio-Michel, Andrea Falqui, Cristiano Di Benedetto, Giancarla Alberti, Vittorio Ricci, Umberto Anselmi-Tamburini, Patrizia Sommi

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20 Scopus citations


CeO2 nanoparticles (CNPs) have been investigated as promising antioxidant agents with significant activity in the therapy of diseases involving free radicals or oxidative stress. However, the exact mechanism responsible for CNP activity has not been completely elucidated. In particular, in situ evidence of modification of the oxidative state of CNPs in human cells and their evolution during cell internalization and subsequent intracellular distribution has never been presented. In this study we investigated modification of the Ce(iii)/Ce(iv) ratio following internalization in human cells by X-ray absorption near edge spectroscopy (XANES). From this analysis on cell pellets, we observed that CNPs incubated for 24 h showed a significant increase in Ce(iii). By coupling on individual cells synchrotron micro-X-ray fluorescence (μXRF) with micro-XANES (μXANES) we demonstrated that the Ce(iii)/Ce(iv) ratio is also dependent on CNP intracellular localization. The regions with the highest CNP concentrations, suggested to be endolysosomes by transmission electron microscopy, were characterized by Ce atoms in the Ce(iv) oxidation state, while a higher Ce(iii) content was observed in regions surrounding these areas. These observations suggest that the interaction of CNPs with cells involves a complex mechanism in which different cellular areas play different roles.
Original languageEnglish (US)
Pages (from-to)1527-1538
Number of pages12
Issue number4
StatePublished - 2017

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank A. Casu (King Adullah University of Science and Technology, Thuwal) for the single-crystal structure analysis and E. Solcia (University of Pavia, Department of Molecular Medicine) for the ultrastructural cell analysis. This work was supported by Fondazione Cariplo (Grants No. 2011-2095).


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