In vitro and in vivo assessment of nanoceria biocompatibility for their safe use in nervous system applications

Abstract

Nanoceria, or cerium dioxide nanoparticles (CeO₂ NP), are increasingly employed in a number of industrial and commercial applications. Hence, the environmental presence of these nanoparticles is growing progressively, enhancing the global concern on their potential health effects. Recent studies suggest that nanoceria may also have promising biomedical applications particularly in neurodegenerative and brain-related pathologies, but studies addressing their toxicity, and specifically on the nervous system, are still scarce, and their potential adverse effects and action mechanism are not totally understood yet. The objective of this work was to assess the biological behaviour of CeO₂ NP in vitro in human nervous systems cells, and in vivo in Drosophila melanogaster to characterize their safety for exposed individuals and verify their suitability to be further employed in diagnosis and treatment of nervous system disorders. Cell cycle alterations, late apoptosis rate and DNA damage (comet and γH2AX assays), were determined in neuronal SH-SY5Y and glial A172 cells treated with nanoceria. Moreover, the survival rate, morphological changes and behavioural alterations were analysed in D. melanogaster individuals chronically exposed to CeO₂ NP. The results obtained from the in vitro assessment showed that the nanoceria generally presented a good biocompatibility with scarce cyto- or genotoxic effects, essentially depending the exposure time and cell type, and being restricted to the longer exposure periods. Nevertheless, decrease in adult size and alterations observed in the larval crawling in the in vivo assays highlight the need of further investigations before establishing clinical uses of nanoceria.

Environmental Implication

Cerium dioxide nanoparticles (CeO₂ NP or nanoceria) are increasingly used in a variety of industrial and commercial applications, mainly as polishing material, environmental remediation agent, automotive diesel fuel additive-combustion catalyst, and electrode material. It was estimated that around 100–1000 tons of CeO₂ NP are being produced per year only in Europe. As a consequence, the quantity of CeO₂ NP annually released into the environment via anthropogenic activities is quite significant. Still, and despite all their uses and potential applications, their potential adverse effects and action mechanism are not totally understood yet.