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

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

Ivana Garcarova 1 Katarina Siposova 1 Yuliia Shlapa 2 Anatolii Belous 2 Eva Valusova 1 Andrey Musatov 1

1Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia
2Department of Solid State Chemistry, V. I. Vernadskii Institute of General and Inorganic Chemistry of the NAS of Ukraine, 32/34 Palladina ave., 03142 Kyiv, Ukraine
garcarova@saske.sk

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. 

This work was supported by the grants: Grant programme for SAS PhD students No. APP0164, VEGA 2/0094/21 and NATO Science for Peace and Security Programme No. G5683.
[1] Lévy E., et al. Int J Mol Sci. 2019, 20(16) 3896.
[2] Labbadia, J., Morimoto, R.I., Annu Rev Biochem. 2015, 84, 435-464.
[3] Das, S., et al. Nanomedicine, 2013, 8 (9), 1483-1508.
[4] Siposova, K., et al. ACS Appl. Bio Mater. 2019, 2, 1884−1896.
[5] Siposova, K., et al. BBA-Proteins and Proteomics, 2019, 1867, 259-274.
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Independent and correlated experiments 22.05.2021 13:02
Thank you for your contribution - the study is touching an interesting and important issue, the abstract is very carefully and professionally prepared and the presentation "proves" a huge amount of...Zobraziť celý komentár
Re: Independent and correlated experiments 25.05.2021 11:20
Thank you for your comment and questions.

CeO2-NPs are used increasingly in nanotechnology and particularly in bioresearch. In bioscience the great attention is paid to CeO2-NPs because of thei...
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Re: Re: Independent and correlated experiments 24.06.2021 06:48
Congratulations!
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