TY - JOUR
T1 - Dependence of the Ce(iii)/Ce(iv) ratio on intracellular localization in ceria nanoparticles internalized by human cells
AU - Ferraro, Daniela
AU - Tredici, Ilenia G.
AU - Ghigna, Paolo
AU - Castillio-Michel, Hiram
AU - Falqui, Andrea
AU - Di Benedetto, Cristiano
AU - Alberti, Giancarla
AU - Ricci, Vittorio
AU - Anselmi-Tamburini, Umberto
AU - Sommi, Patrizia
N1 - 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).
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/622724
UR - http://pubs.rsc.org/en/Content/ArticleLanding/2017/NR/C6NR07701C#!divAbstract
UR - http://www.scopus.com/inward/record.url?scp=85010953500&partnerID=8YFLogxK
U2 - 10.1039/c6nr07701c
DO - 10.1039/c6nr07701c
M3 - Article
C2 - 28067927
SN - 2040-3364
VL - 9
SP - 1527
EP - 1538
JO - Nanoscale
JF - Nanoscale
IS - 4
ER -
