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Effects of Different Cerium Oxide Nanoparticle Formulations on Oxidative Stress Survival in the Nematode C. elegans

Cerium oxide (CeO2) nanoparticles (CeNPs or nanoceria) are potent antioxidants that are being explored as a potential therapeutic for diseases in which oxidative stress plays an important pathological role. Nanoceria catalytically neutralize multiple types of reactive oxygen species. However, both therapeutic and toxic effects of CeNPs have been reported. We hypothesize that these disparate reports are due to small differences in each type of nanoparticle arising from the synthetic process. These small differences could lead to particles that aggregate and induce toxicity versus particles that are monodispersed and display antioxidant properties. Due to its short lifespan and easily observable behaviors, we used the nematode worm C. elegans to examine, in parallel, the effects of three different types of cerium oxide nanoparticle formulations on survival after exposure to oxidative stress. To induce oxidative stress, we used juglone (5‐hydroxy‐1,4‐naphthoquinone), a compound derived from many plant species including the black walnut tree, Juglans nigra. We first conducted a dose‐response analysis to find a concentration of juglone that induced significant mortality in our model system. This dose of juglone, 250 μM, was then used in subsequent experiments to test the impact of nanoparticle pre‐treatment on worm viability. For these studies, animals were fed, starting at the L1 larval stage, a range of doses (0 to 580 μM) of three formulations of nanoceria that differed in size as well as the stabilizers used during synthesis. When the worms reached young adulthood, they were exposed to 250 μM juglone for 1 hour. Worms were then placed back onto fresh growth plates containing nanoceria and animal viability was determined 24 hr later via a nose‐touch assay conducted by an experimenter blind to treatment. Preliminary analysis shows that the three different formulations tested showed varying potency in protecting C. elegans from juglone‐induced oxidative stress, supporting our hypothesis that differences in synthetic parameters can impact the ultimate biological effect of the nanoparticles.