Dual-functional selenium nanoparticles bind to and inhibit amyloid β fiber formation in Alzheimer's disease.

Inhibition of amyloid β (Aβ) aggregation holds considerable promise as a therapeutic strategy for Alzheimer's disease (AD). However, successful inhibition is hard to achieve due to the blood-brain barrier (BBB) and the non-selective distribution of drugs. Herein, two targeting peptides (LPFFD and TGN) were conjugated to selenium nanoparticles (SeNPs). We found that the concentration ratio of LPFFD to TGN taken as 1 : 1 could form the most effective dual-functional SeNPs (L1T1-SeNPs) for inhibiting Aβ aggregation and crossing the BBB. L1T1-SeNPs can cross the BBB and have a strong affinity toward Aβ species, and thus, they can efficiently suppress extracellular Aβ fibrillation by disrupting hydrophobic and electrostatic interactions that are important for Aβ40 nucleation. Also, L1T1-SeNPs can suppress the Aβ40 fiber mediated generation of reactive oxygen species (ROS) and their corresponding neurotoxicity in PC12 cells. In addition, L1T1-SeNPs exert synergistic effects on the inhibition of Aβ aggregation and cross the BBB efficiently. Collectively, these results demonstrate that dual-functional SeNPs might be a valuable targeting system for inhibiting Aβ aggregation.