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.