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表面修饰的二氧化铈纳米颗粒,具有改善的抗淀粉样蛋白和保留的纳米酶活性。

Surface-modified cerium dioxide nanoparticles with improved anti-amyloid and preserved nanozymatic activity.

机构信息

Department of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 040 01 Kosice, Slovakia.

Department of Solid-State Chemistry, V. I. Vernadsky Institute of General & Inorganic Chemistry of the NAS of Ukraine, 32/34 Palladina ave., Kyiv 03142, Ukraine.

出版信息

Colloids Surf B Biointerfaces. 2023 Jul;227:113356. doi: 10.1016/j.colsurfb.2023.113356. Epub 2023 May 15.

Abstract

Cerium dioxide nanoparticles (CeO NPs) are used increasingly in nanotechnology and particularly in biotechnology and bioresearch. Thus, CeO NPs have been successfully tested in vitro as a potential therapeutic agent for various pathologies associated with oxidative stress, including the formation of protein amyloid aggregates. In this study, to increase the anti-amyloidogenic efficiency and preserve the antioxidant potential, the surface of the synthesized CeO NPs is modified with a nonionic, sugar-based surfactant, dodecyl maltoside (DDM), which is known for its high anti-amyloidogenic activity and biocompatibility. Dynamic light scattering and Fourier transform infrared spectroscopy demonstrated successful modification by DDM. The apparent hydrodynamic diameters of CeO NPs and DDM-modified NPs (CeO@DDM NPs) are found to be ⁓180 nm and ⁓260 nm, respectively. A positive zeta potential value of + 30.5 mV for CeO NPs and + 22.5 mV for CeO @DDM NPs suggest sufficient stability and good dispersion of NPs in an aqueous solution. A combination of Thioflavin T fluorescence analysis and atomic force microscopy is used to assess the effect of nanoparticles on the formation of insulin amyloid fibrils. Results show that the fibrillization of insulin is inhibited by both, naked and modified NPs in a dose-dependent manner. However, while the IC of naked NPs is found to be ∼270 ± 13 µg/mL, the surface-modified NPs are 50% more efficient with IC equaled to 135 ± 7 µg/mL. In addition, both, the naked CeO NPs and DDM-modified NPs displayed an antioxidant activity expressed as oxidase-, catalase- and SOD-like activity. Therefore, the resulting nanosized material is very well suited to prove or disprove the hypothesis that oxidative stress plays a role in the formation of amyloid fibrils.

摘要

二氧化铈纳米粒子(CeO NPs)在纳米技术中得到了越来越广泛的应用,特别是在生物技术和生物研究中。因此,CeO NPs 已成功在体外作为各种与氧化应激相关的病理学的潜在治疗剂进行测试,包括蛋白质淀粉样纤维聚集体的形成。在这项研究中,为了提高抗淀粉样形成效率并保持抗氧化潜力,合成的 CeO NPs 的表面用非离子型、基于糖的表面活性剂十二烷基麦芽糖(DDM)进行修饰,DDM 以其高抗淀粉样形成活性和生物相容性而闻名。动态光散射和傅里叶变换红外光谱表明 DDM 成功修饰。CeO NPs 和 DDM 修饰的 NPs(CeO@DDM NPs)的表观水动力学直径分别为 ⁓180nm 和 ⁓260nm。CeO NPs 的正zeta 电位值为 +30.5mV,CeO@DDM NPs 的正zeta 电位值为 +22.5mV,这表明 NPs 在水溶液中具有足够的稳定性和良好的分散性。使用 Thioflavin T 荧光分析和原子力显微镜组合来评估纳米粒子对胰岛素淀粉样纤维形成的影响。结果表明,裸纳米粒子和修饰纳米粒子都以剂量依赖的方式抑制胰岛素的纤维化。然而,当裸 NPs 的 IC 被发现为约 270 ± 13 µg/mL 时,表面修饰的 NPs 的效率提高了 50%,IC 等于 135 ± 7 µg/mL。此外,裸 CeO NPs 和 DDM 修饰的 NPs 均表现出抗氧化活性,表现为氧化酶、过氧化氢酶和 SOD 样活性。因此,所得纳米材料非常适合证明或反驳氧化应激在淀粉样纤维形成中起作用的假设。

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