Cerium oxide nanoparticles (CeO₂ NPs) are well known for their application in various fields of industry, as well as in biology and medicine. Knowledge of synthesis schemes, physicochemical and morphological features of nanoscale CeO₂ is important for assessing their antioxidant behavior and understanding the mechanism of oxidative stress and its consequences. The choice of the method of synthesis should be based on the possibility to choose the conditions and parameters for obtaining CeO₂ with controlled dimensions and a ratio of Се³⁺/Се⁴⁺ on their surface. In this study, CeO₂ NPs are synthesized by precipitation in mixed water-alcohol solutions at constant pH = 9. The properties of obtained NPs are studied using various methods of physical-chemical characterization such as X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. The size of CeO₂ NPs varied from 14 to 4.2 nm with increasing alcohol concentration, while the effect of constant pH during synthesis on the morphology of the particles was insignificant. The synthesized nanoparticles form highly stable aqueous suspensions since their zeta-potential is higher than + 40 mV. It is found that the ability of CeO₂ NPs to self-stabilize is associated with the presence of hydrated Ce⁴⁺ ions on their surface. In vitro biological studies have shown that, regardless of particle size, CeO₂ NPs have antioxidant potential, but smaller NPs with a higher percentage of Ce³⁺ on the surface had a more effective antioxidant effect. In addition, the size-depended activity of CeO₂ NPs to inhibit the amyloid formation of insulin is demonstrated.

Oxidative stress is known to be associated with a number of degenerative diseases. A better knowledge of the interplay between oxidative stress and amyloidogenesis is crucial for the understanding of both, aging and age-related neurodegenerative diseases. Cerium dioxide nanoparticles (CeO₂ NPs, nanoceria) due to their remarkable properties are perspective nanomaterials in the study of the processes accompanying oxidative-stress-related diseases, including amyloid-related pathologies. In the present work, we analyze the effects of CeO₂ NPs of different sizes and Ce⁴⁺/Ce³⁺ ratios on the fibrillogenesis of insulin, SOD-like enzymatic activity, oxidative stress, biocompatibility, and cell metabolic activity. CeO₂ NPs (marked as Ce1–Ce5) with controlled physical–chemical parameters, such as different sizes and various Ce⁴⁺/Ce³⁺ ratios, are synthesized by precipitation in water–alcohol solutions. All synthesized NPs are monodispersed and exhibit good stability in aqueous suspensions. ThT and ANS fluorescence assays and AFM are applied to monitor the insulin amyloid aggregation and antiamyloid aggregation activity of CeO₂ NPs. The analyzed Ce1–Ce5 nanoparticles strongly inhibit the formation of insulin amyloid aggregates in vitro. The bioactivity is analyzed using SOD and MTT assays, Western blot, fluorescence microscopy, and flow cytometry. The antioxidative effects and bioactivity of nanoparticles are size- or valence-dependent. CeO₂ NPs show great potential benefits for studying the interplay between oxidative stress and amyloid-related diseases, and can be used for verification of the role of oxidative stress in amyloid-related diseases.