Evaluation of anti-amyloid and anti-oxidative activity of naked and surface-modified CeO2 nanoparticles

Loss of protein homeostasis is a common feature of aging and diseases that are characterized by the appearance of nonnative protein aggregates in various tissues [1]. One of the currently accepted theories is that oxidative stress is associated with aging and age-related neurodegenerative disorders [1,2]. In bioscience the great attention is paid to cerium dioxide nanoparticles (CeO₂-NPs) because of their antioxidant properties, i.e. CeO₂-NPs possess the enzymatic mimetic activities in a redox-dependent manner [3].

The aim of this study was to prepare CeO₂-NPs which will retain antioxidant properties, but also demonstrate significant anti-amyloidogenic activity.

CeO₂-NPs were synthesized by precipitation from reversal microemulsions and characterized as described previously [4]. Naked CeO₂-NPs possess crystalline structure, small 8 – 10 nm sizes, were stable, and non-agglomerated as confirmed by X-ray, DLS, TEM and AFM. Synthesized NPs were functionalized by non-ionic detergent dodecyl maltoside (CeO₂-NPs@DDM). Anti-oxidant activity of CeO₂-NPs and CeO₂-NPs@DDM was evaluated by monitoring their peroxidase/catalase activity. We observed that CeO₂-NPs are capable to effectively decompose H₂O₂, monitored via N, N-diethyl-p-phenylenediamine sulphate assay. As expected, the higher catalase/peroxidase activity was detected for the naked CeO₂-NPs, but CeO₂-NPs@DDM still remain catalase/peroxidase activity. Thioflavin T (ThT) and 1-Anilinonaphyhalene-8-sulfonic acid (ANS) fluorescence assay, and atomic force microscopy (AFM) have been employed to investigate the amyloid aggregation of insulin in the absence and presence of NPs. We have demonstrated that fibrillization of insulin is inhibited by both, naked and coated NPs in a dose-dependent manner. The data suggest that the NPs surface modification by DDM led to enhanced inhibiting activity. In addition, anti-amyloidogenic activity could be significantly enhanced by further functionalization of CeO₂-NPs@DDM (for example by using natural polyphenol, rottlerin [5]). 

We concluded, that CeO₂-NPs have a potential for proving or disproving the hypothesis that oxidative stress plays a crucial role in the development of age-related diseases associated with the pathological aggregation of proteins. Although the exact mechanism of protein-nanoparticles interaction is not understood, our findings may stimulate further experiments to elucidate the molecular details of the nanoparticle effect and enhance our understanding of the fibrillization process.