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Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model

[Image: see text] Both cerium oxide (CeOx) nanoparticles and mefenamic acid (MFA) are known anti-inflammatory agents with hepatoprotective properties and are therefore prescribed for one of the major diseases in the world, nonalcoholic fatty liver disease (NAFLD). To study the potential cytotoxicity...

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Autores principales: Eilenberger, Christoph, Selinger, Florian, Rothbauer, Mario, Lin, Yiji, Limbeck, Andreas, Schädl, Barbara, Grillari, Johannes, Kavok, Nataliya S., Klochkov, Vladimir K., Malyukin, Yuri V., Margitich, Victor, Ertl, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887746/
https://www.ncbi.nlm.nih.gov/pubmed/33615164
http://dx.doi.org/10.1021/acsptsci.0c00170
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author Eilenberger, Christoph
Selinger, Florian
Rothbauer, Mario
Lin, Yiji
Limbeck, Andreas
Schädl, Barbara
Grillari, Johannes
Kavok, Nataliya S.
Klochkov, Vladimir K.
Malyukin, Yuri V.
Margitich, Victor
Ertl, Peter
author_facet Eilenberger, Christoph
Selinger, Florian
Rothbauer, Mario
Lin, Yiji
Limbeck, Andreas
Schädl, Barbara
Grillari, Johannes
Kavok, Nataliya S.
Klochkov, Vladimir K.
Malyukin, Yuri V.
Margitich, Victor
Ertl, Peter
author_sort Eilenberger, Christoph
collection PubMed
description [Image: see text] Both cerium oxide (CeOx) nanoparticles and mefenamic acid (MFA) are known anti-inflammatory agents with hepatoprotective properties and are therefore prescribed for one of the major diseases in the world, nonalcoholic fatty liver disease (NAFLD). To study the potential cytotoxicity and anti-inflammatory effects as well as drug retention of a potential therapeutic CeOx/MFA supramolecular complex, a well-standardized hepatic (HepG2) spheroid model was used. Results showed that the highest cytotoxicity for the CeOx/MFA supramolecular complex was found at 50 μg/mL, while effective doses of 0.1 and 1 μg/mL yielded a significant decrease of TNF-α and IL-8 secretion. Time-resolved analysis of HepG2 spheroids revealed a spatiotemporal distribution of the supramolecular complex and limited clearance from the internal microtissue over a period of 8 days in cultivation. In summary, our results point at rapid uptake, distribution, and biostability of the supramolecular complex within the HepG2 liver spheroid model as well as a significant anti-inflammatory response at noncytotoxic levels.
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spelling pubmed-78877462021-12-08 Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model Eilenberger, Christoph Selinger, Florian Rothbauer, Mario Lin, Yiji Limbeck, Andreas Schädl, Barbara Grillari, Johannes Kavok, Nataliya S. Klochkov, Vladimir K. Malyukin, Yuri V. Margitich, Victor Ertl, Peter ACS Pharmacol Transl Sci [Image: see text] Both cerium oxide (CeOx) nanoparticles and mefenamic acid (MFA) are known anti-inflammatory agents with hepatoprotective properties and are therefore prescribed for one of the major diseases in the world, nonalcoholic fatty liver disease (NAFLD). To study the potential cytotoxicity and anti-inflammatory effects as well as drug retention of a potential therapeutic CeOx/MFA supramolecular complex, a well-standardized hepatic (HepG2) spheroid model was used. Results showed that the highest cytotoxicity for the CeOx/MFA supramolecular complex was found at 50 μg/mL, while effective doses of 0.1 and 1 μg/mL yielded a significant decrease of TNF-α and IL-8 secretion. Time-resolved analysis of HepG2 spheroids revealed a spatiotemporal distribution of the supramolecular complex and limited clearance from the internal microtissue over a period of 8 days in cultivation. In summary, our results point at rapid uptake, distribution, and biostability of the supramolecular complex within the HepG2 liver spheroid model as well as a significant anti-inflammatory response at noncytotoxic levels. American Chemical Society 2020-12-08 /pmc/articles/PMC7887746/ /pubmed/33615164 http://dx.doi.org/10.1021/acsptsci.0c00170 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Eilenberger, Christoph
Selinger, Florian
Rothbauer, Mario
Lin, Yiji
Limbeck, Andreas
Schädl, Barbara
Grillari, Johannes
Kavok, Nataliya S.
Klochkov, Vladimir K.
Malyukin, Yuri V.
Margitich, Victor
Ertl, Peter
Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model
title Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model
title_full Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model
title_fullStr Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model
title_full_unstemmed Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model
title_short Cytotoxicity, Retention, and Anti-inflammatory Effects of a CeO(2) Nanoparticle-Based Supramolecular Complex in a 3D Liver Cell Culture Model
title_sort cytotoxicity, retention, and anti-inflammatory effects of a ceo(2) nanoparticle-based supramolecular complex in a 3d liver cell culture model
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887746/
https://www.ncbi.nlm.nih.gov/pubmed/33615164
http://dx.doi.org/10.1021/acsptsci.0c00170
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