Se/Ru nanoparticles as inhibitors of metal-induced Aβ aggregation in Alzheimer's disease

Abstract

Amyloid β (Aβ) aggregates are considered as possible targets for therapy of Alzheimer's disease (AD). Metal ions play an important role in amyloid aggregation and neurotoxicity in the AD pathogenesis. Disruption of the interactions between these metal ions and peptides holds considerable promise as a therapeutic strategy for AD treatment. In this study, L-Cys-modified Se/Ru nanoparticles (NPs) have been designed as Aβ-binding units to inhibit metal-induced Aβ aggregation. L-Cys was used as both the reducing agent and surface modifier in the formation of SeNPs, RuNPs and Se/RuNPs. We found that RuNPs and Se/RuNPs have a strong affinity toward Aβ species and efficiently suppress extracellular Aβ₄₀ self-assembly and Zn²⁺-induced fibrillization. Also, Se/RuNPs can suppress the Zn²⁺–Aβ₄₀ mediated generation of reactive oxygen species (ROS) and their corresponding neurotoxicity in PC12 cells. Intriguingly, SeNPs do not have the same ability as Se/RuNPs. In addition, Se/RuNPs also decrease intracellular Aβ₄₀ fibrillization, but this process does not involve the lysosomal pathway. These results suggest that ruthenium significantly enhances the activity of Se/RuNPs binding to Aβ₄₀. This interaction would block the Zn²⁺ binding to Aβ₄₀ peptides and lower the concentration of the free monomer, thus decreasing fibrillization. Owing to this, Se/RuNPs may represent a new strategy in AD treatment.