Chiral gold nanoparticles enantioselectively rescue memory deficits in a mouse model of Alzheimer’s disease

作者：Ke Hou, Jing Wei Zhao, Hui Wang, Bin Li, Kexin Li, Xinghua Shi, Kaiwei Wan, Jing Ai, Jiawei Lv, Dawei Wang, Qunxing Huang, Huayi Wang, Qin Cao, Shaoqin Liu, Zhiyong Tang · 发表于：Nature Communications · 年份：2020 · DOI：10.1038/s41467-020-18525-2 · 被引用次数：366 · 研究领域：Alzheimer's disease research and treatments、Nanocluster Synthesis and Applications、Drug Transport and Resistance Mechanisms

Preventing aggregation of amyloid beta (Aβ) peptides is a promising strategy for the treatment of Alzheimer's disease (AD), and gold nanoparticles have previously been explored as a potential anti-Aβ therapeutics. Here we design and prepare 3.3 nm L- and D-glutathione stabilized gold nanoparticles (denoted as L3.3 and D3.3, respectively). Both chiral nanoparticles are able to inhibit aggregation of Aβ42 and cross the blood-brain barrier (BBB) following intravenous administration without noticeable toxicity. D3.3 possesses a larger binding affinity to Aβ42 and higher brain biodistribution compared with its enantiomer L3.3, giving rise to stronger inhibition of Aβ42 fibrillation and better rescue of behavioral impairments in AD model mice. This conjugation of a small nanoparticle with chiral recognition moiety provides a potential therapeutic approach for AD.