Shifts in oxidation states of cerium oxide nanoparticles detected inside intact hydrated cells and organelles

Abstract

Cerium oxide nanoparticles (CNPs) have been shown to induce diverse biological effects, ranging from toxic to beneficial. The beneficial effects have been attributed to the potential antioxidant activity of CNPs via certain redox reactions, depending on their oxidation state or Ce3+/Ce4+ ratio. However, this ratio is strongly dependent on the environment and age of the nanoparticles and it is unclear whether and how the complex intracellular environment impacts this ratio and the possible redox reactions of CNPs. To identify any changes in the oxidation state of CNPs in the intracellular environment and better understand their intracellular reactions, we directly quantified the oxidation states of CNPs outside and inside intact hydrated cells and organelles using correlated scanning transmission x-ray and super resolution fluorescence microscopies. By analyzing hundreds of small CNP aggregates, we detected a shift to a higher Ce3+/Ce4+ ratio in CNPs inside versus outside the cells, indicating a net reduction of CNPs in the intracellular environment. We further found a similar ratio in the cytoplasm and in the lysosomes, indicating that the net reduction occurs earlier in the internalization pathway. Together with oxidative stress and toxicity measurements, our observations identify a net reduction of CNPs in the intracellular environment, which is consistent with their involvement in potentially beneficial oxidation reactions, but also point to interactions that can negatively impact the health of cells.

Intracellularly Disintegratable Polysulfoniums for Efficient Gene Delivery

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The Chameleon Effect: Characterization Challenges Due to the Variability of Nanoparticles and Their Surfaces

“…As the oxidizing power of the solution lowered the particles switched from the +4 to the +3 state (Kuchibhatla et al, 2012 ). Changes or variations in the oxidation state of ceria NPs have also been observed within intact hydrated cells and organelles (Szymanski et al, 2015 ).…”

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Synthesis of Cerium Oxide Nanoparticles Using Various Methods: Implications for Biomedical Applications

“…This suggests that a noticeable reduction of the cerium oxide nanoparticles occurs in the cells. The authors postulate that differences in pH of the endocytic vesicles (pH = 7.4) versus lysosome (pH = 4.5) may also be the reason for these differences in surface chemistry [50]. Qi and company synthesized PPEG (Phosphonated-Polyethylene glycol oligomers) surface modified nano-powder for re-dispersion in aqueous solutions.…”