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

Author:

Hou Ke,Zhao Jing,Wang Hui,Li Bin,Li Kexin,Shi XinghuaORCID,Wan KaiweiORCID,Ai Jing,Lv Jiawei,Wang Dawei,Huang Qunxing,Wang Huayi,Cao Qin,Liu Shaoqin,Tang ZhiyongORCID

Abstract

AbstractPreventing 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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