Self-assembled cysteine-copper chiral nanoparticles for inhibiting aggregation of amyloid β peptides

Inhibiting the aggregation of amyloid β (Aβ) peptides is a promising strategy for the treatment of Alzheimer's disease (AD). However, there have been very limited reports of highly effective inhibitors of Aβ aggregation in the past few decades. Herein, two types of nanoparticles (NPs) with opposite chirality were prepared through one-step assembly of L-cysteine (L-Cys) or D-cysteine (D-Cys) and Cu²⁺ at room temperature. L-Cys-Cu NPs and D-Cys-Cu NPs were able to inhibit the aggregation of Aβ₄₂. Compared to their enantiomer L-Cys-Cu NPs, D-Cys-Cu NPs showed a larger binding affinity to Aβ₄₂, leading to stronger inhibition of Aβ₄₂ fibrillation. Moreover, D-Cys-Cu NPs were found to cause the disaggregation of Aβ₄₂ fibrils. Due to their simple preparation, good biocompatibility and significant effects, these chiral Cys-Cu NPs have great potential in inhibiting protein aggregation.