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

Abstract

Cerium dioxide nanoparticles (CeO₂ NPs) are used increasingly in nanotechnology and particularly in biotechnology and bioresearch. Thus, CeO₂ 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 CeO₂ 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 CeO₂ NPs and DDM-modified NPs (CeO₂@DDM NPs) are found to be ⁓180 nm and ⁓260 nm, respectively. A positive zeta potential value of + 30.5 mV for CeO₂ NPs and + 22.5 mV for CeO₂ @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 IC₅₀ of naked NPs is found to be ∼270 ± 13 µg/mL, the surface-modified NPs are 50% more efficient with IC₅₀ equaled to 135 ± 7 µg/mL. In addition, both, the naked CeO₂ 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.

Keywords: Amyloid aggregation; Cerium dioxide nanoparticles; Nanozymes; Surface modification; Surfactant.