Siposova Katarina, Huntosova Veronika, Garcarova Ivana, Shlapa Yuliia, Timashkov Illia, Belous Anatolii, Musatov Andrey
Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 04001 Kosice, Slovakia.
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P.J. Safarik University in Kosice, Jesenna 5, 04154 Kosice, Slovakia.
Biomedicines. 2022 Apr 19;10(5):942. doi: 10.3390/biomedicines10050942.
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 (CeO 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 CeO NPs of different sizes and Ce/Ce ratios on the fibrillogenesis of insulin, SOD-like enzymatic activity, oxidative stress, biocompatibility, and cell metabolic activity. CeO NPs (marked as Ce1-Ce5) with controlled physical-chemical parameters, such as different sizes and various Ce/Ce 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 CeO 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. CeO 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.
已知氧化应激与多种退行性疾病有关。深入了解氧化应激与淀粉样蛋白生成之间的相互作用对于理解衰老和与年龄相关的神经退行性疾病至关重要。二氧化铈纳米颗粒（CeO NPs，纳米氧化铈）因其卓越的性能，在研究与氧化应激相关疾病（包括淀粉样蛋白相关病理）的伴随过程中是很有前景的纳米材料。在本工作中，我们分析了不同尺寸和Ce/Ce比的CeO NPs对胰岛素纤维形成、超氧化物歧化酶（SOD）样酶活性、氧化应激、生物相容性和细胞代谢活性的影响。通过在水 - 醇溶液中沉淀合成具有可控物理化学参数（如不同尺寸和各种Ce/Ce比）的CeO NPs（标记为Ce1 - Ce5）。所有合成的NPs都是单分散的，并且在水悬浮液中表现出良好的稳定性。应用硫黄素T（ThT）和1 - 苯胺基萘 - 8 - 磺酸（ANS）荧光测定法以及原子力显微镜（AFM）来监测胰岛素淀粉样聚集和CeO NPs的抗淀粉样聚集活性。所分析的Ce1 - Ce5纳米颗粒在体外强烈抑制胰岛素淀粉样聚集体的形成。使用SOD和MTT测定法、蛋白质免疫印迹法、荧光显微镜和流式细胞术分析生物活性。纳米颗粒的抗氧化作用和生物活性取决于尺寸或价态。CeO NPs在研究氧化应激与淀粉样蛋白相关疾病之间的相互作用方面显示出巨大的潜在益处，并且可用于验证氧化应激在淀粉样蛋白相关疾病中的作用。
