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

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

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PoužívateľVedecká prácaDizajnDiskusná interakcia
RNDr. Dajana Rucova Dajana Rucova PhD.100%100%-
Bc. Daniela Máčalová100%100%100%
RNDr. Ing. Katarína Šipošová PhD.100%100%100%
ISBN: ISBN 978-80-972360-7-6

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

Ivana Garcarova1 , Katarina Siposova , Yuliia Shlapa2 , Anatolii Belous , Eva Valusova , Andrey Musatov ,
1 Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia
2 Department 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. 

Poďakovanie: 

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.

Zdroje: 

[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.

Diskusia

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 experimental work done using various techniques and methods. For the latter mentioned it would have been better to present the results in the form of a short communication or a ppt presentation. The poster has limited space (moreover, its design with all the collours is somewhat distracting ;) As a consequence, the poster presents what the results are but not quite what they mean.
The reason might lie in the intent to publish the findings as a part of an original paper (?)

Ad to the first point in the conclusion part "CeO2-NPs were prepared, succesfully modified with dodecyl maltoside and characterized", I would like to ask: how many independent preparation were measured and whether the measurements of different responses (using different methods) were performed on the same preparations (if so, the pattern of associations between the changes might be explored). Thanks.
iwa

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 their antioxidant properties, i.e. CeO2-NPs possess ability for multi-enzymatic scavenging of reactive oxygen species, exhibit superoxide dismutase and catalase enzymes mimetic activities in a redox-state dependent manner. Recently, we have demonstrated antiamyloidogenic effect of “naked” CeO2-NPs. However, the antiamyloidogenic effect of “naked” CeO2-NPs is not as strong as some other NPs (carbon dots) or organic compounds (phospholipids/detergents).
On the other hand, their clinical translation requires a significant improvement of their surface properties, particularly through the development of an appropriate functionalization. Control of interfacial properties is a central issue in nanoparticle’s development to increase their biocompatibility, stability in biological media. In addition, nanoceria’s coating strongly influences cellular uptake and cytotoxicity. The objective of our study was to prepare CeO2-NPs with enhanced anti-amyloidogenic activity while retaining their antioxidant properties and decreasing their cytotoxicity.
As part of the characterization of modified CeO2-NPs @ DDM, we performed the following measurements: DLS - Hydrodynamic diameter measurement and Zeta potential measurement, Infrared with Fourier transform and UV-VIS measurements. In our experiments, the presented values represent the average of at least three independent measurements. In future, we are planning perform more detailed analysis, including for example thermal/thermogravimetric analysis and in collaboration also small-angle scattering measurements.

Congratulations!
iwa