(338c) Nanoceria Morphology Dictates Metabolic Impairment in Primary Hepatocytes

Cerium oxide nanoparticles, or nanoceria, have applications in fuel cells, catalysis, and polishing in numerous industries because of their redox properties. With their antioxidant ability, nanoceria have also emerged as potential disease therapeutics with beneficial effects demonstrated in various experimental settings. Nanoceria treatment has been studied in models of liver disease including fibrosis, nonalcoholic fatty liver disease, and hepatocellular carcinoma with some evidence of benefit. However, concerns of nanoparticle-induced toxicity remain with varied results in the literature. Employment of nanoceria with polyhedral morphology is most common, but nanoparticle size and morphology can differ across studies. This is noteworthy, as such properties are known to influence cellular uptake and biological response. To study the potential effects of ceria with different nanomorphologies on liver function and cytotoxicity, we cultured primary hepatocytes with ceria nanorods, nanocubes, and bulk ceria. Hepatocyte morphology and viability varied in response to the different nanoceria, with decreased cell viability resulting from nanorod and bulk ceria exposure, but not nanocubes. The essential hepatic functions of urea and albumin secretion were reduced by nanoceria treatment. No significant shape-dependent effects were observed in urea secretion, whereas albumin secretion was substantially decreased by bulk ceria and nanorods. Hepatocytes exposed to nanocubes best maintained albumin secretion. Cytochrome P450 activity, critical to hepatocyte metabolism, was similarly maintained following ceria nanocubes exposure but significantly reduced by nanorods and bulk ceria. Finally, hepatocytes cultured with ceria nanorods showed upregulated LC3B protein expression, suggesting autophagic stress as a mediator of impaired cell viability and hepatic function. Together our results indicate various shape-dependent effects of nanoceria on hepatocytes and identify cube-like nanoceria as best at preserving key hepatic functions in vitro, a potential consideration for future work exploring nanoceria-based disease treatments.