Enantiomers of cysteine-modified SeNPs (D/LSeNPs) as inhibitors of metal-induced Aβ aggregation in Alzheimer's disease

Chiral molecules, which selectively target and inhibit amyloid beta-peptide (A beta) aggregation, have potential use as therapeutic agents for the treatment of Alzheimer's disease (AD). Here we use cysteine enantiomer-modified SeNPs (abbreviated as D/LSeNPs) to demonstrate that surface chirality strongly influences the formation of A beta aggregates in the presence of metal ions, such as Zn2+ or Cu2+. The two chiral molecule modified nanoparticles could inhibit the formation of A beta fibrils by binding A beta, thus blocking the formation of A beta fibrils and blocking the metal binding sites. Of the two enantiomers, D/SeNPs appear to more effectively inhibit A beta fibril formation due to a greater affinity for A beta than that of L/SeNPs. Additionally, D/LSeNPs appeared to reduce A beta and metal ion-induced neurotoxicity. Treatment with D/LSeNPs can also decrease the levels of intracellular reactive oxygen species, and stabilize the mitochondrial membrane potential. Of the two enantiomers, D/SeNPs were more effective in protecting the cells than L/SeNPs, and this could be due to D/SeNPs being selectively absorbed by PC12 cells, maintaining cellular redox potentials, and protecting cells against oxidative stress to a greater extent than L/SeNPs. From these results, it appears that chiral molecules can bring novel insight into better drug treatment designs for Alzheimer's disease.