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Stress reaction of kidney epithelial cells to inorganic solid-core nanoparticles

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Abstract

A route of accumulation and elimination of therapeutic engineered nanoparticles (NPs) may be the kidney. Therefore, the interactions of different solid-core inorganic NPs (titanium-, silica-, and iron oxide-based NPs) were studied in vitro with the MDCK and LLC-PK epithelial cells as representative cells of the renal epithelia. Following cell exposure to the NPs, observations include cytotoxicity for oleic acid-coated iron oxide NPs, the production of reactive oxygen species for titanium dioxide NPs, and cell depletion of thiols for uncoated iron oxide NPs, whereas for silica NPs an apparent rapid and short-lived increase of thiol levels in both cell lines was observed. Following cell exposure to metallic NPs, the expression of the tranferrin receptor/CD71 was decreased in both cells by iron oxide NPs, but only in MDCK cells by titanium dioxide NPs. The tight association, then subsequent release of NPs by MDCK and LLC-PK kidney epithelial cells, showed that following exposure to the NPs, only MDCK cells could release iron oxide NPs, whereas both cells released titanium dioxide NPs. No transfer of any solid-core NPs across the cell layers was observed.

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Abbreviations

Carboxy-H2DCFDA:

5/6-Carboxy-2,7-dichloro-dihydro-fluorescein

DAPI:

4′,6′-Diamidino-2-phenylindole

DLS:

Dynamic light scattering

HBSS:

Hank’s buffer solution

3H-T:

Tritiated thymidine

LY:

Lucifer Yellow

MTT:

3,4,5-Dimethylthiazol-yl-2,5-diphenyl tetrazolium bromide

NEM:

N-Ethyl-maleimide

NPs:

Nanoparticles

ROS:

Reactive oxygen species

TBHP:

tert-Butyl hydroperoxide

TEER:

Transepithelial electrical resistance

TEM:

Transmission electron microscopy

USPIO:

Ultrasmall superparamagnetic iron oxide

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Acknowledgments

The authors thank S. Güney-Ayra for excellent technical assistance and P. Bowen and H. Hofmann from EPFL, Lausanne, for providing the thermogravimetric analyses of the silica nanoparticles. This research was supported by a grant from the European Community 7th Framework Program (project no. 2007–201335 “NanoTEST”).

Conflict of interest

The authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest or conflict concerning the information presented in this manuscript.

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Correspondence to Lucienne Juillerat-Jeanneret.

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Halamoda Kenzaoui, B., Chapuis Bernasconi, C. & Juillerat-Jeanneret, L. Stress reaction of kidney epithelial cells to inorganic solid-core nanoparticles. Cell Biol Toxicol 29, 39–58 (2013). https://doi.org/10.1007/s10565-012-9236-8

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