title: Dependence of the Ce(iii)/Ce(iv) ratio on intracellular localization in ceria nanoparticles internalized by human cells.
abstract: CeO2nanoparticles (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.
authors.affiliation: Department of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, Italy. patrizia.sommi@unipv.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ferraro
authors.affiliation: Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
authors.forename: Ilenia G
authors.initials: IG
authors.lastname: Tredici
authors.affiliation: Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghigna
authors.forename: Hiram
authors.initials: H
authors.lastname: Castillo-Michel
authors.affiliation: Biological and Environmental Sciences and Engineering Division, King Adullah University of Science and Technology, 23955-6900 Thuwal, Saudi Arabia.
authors.forename: Andrea
authors.identifier: 0000-0002-1476-7742
authors.initials: A
authors.lastname: Falqui
authors.affiliation: Biological and Environmental Sciences and Engineering Division, King Adullah University of Science and Technology, 23955-6900 Thuwal, Saudi Arabia.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Di Benedetto
authors.affiliation: Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
authors.forename: Giancarla
authors.initials: G
authors.lastname: Alberti
authors.affiliation: Department of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, Italy. patrizia.sommi@unipv.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ricci
authors.affiliation: Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Anselmi-Tamburini
authors.affiliation: Department of Molecular Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia, Italy. patrizia.sommi@unipv.it.
authors.forename: Patrizia
authors.identifier: 0000-0002-8749-2866
authors.initials: P
authors.lastname: Sommi
mesh_terms: D002563:Cerium / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D056928:X-Ray Absorption Spectroscopy
chemical_list: D002563:Cerium