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

• Published in: ACS pharmacology & translational science 2021-02, Vol.4 (1), p.101-106
• Main Authors: 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
• Format: Article
• Language: English
• ISSN: 2575-9108; 2575-9108
• DOI: 10.1021/acsptsci.0c00170

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.