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.

防止淀粉样蛋白 β (Aβ) 肽的聚集是治疗阿尔茨海默病 (AD) 的一种很有前景的策略，而金纳米粒子以前已被探索为一种潜在的抗 Aβ 疗法。在这里，我们设计并制备了 3.3 nm L-和 D-谷胱甘肽稳定的金纳米粒子（分别表示为 L3.3 和 D3.3）。两种手性纳米颗粒都能够抑制 Aβ42 的聚集并在静脉给药后穿过血脑屏障 (BBB)，而没有明显的毒性。与其对映异构体 L3.3 相比，D3.3 对 Aβ42 具有更大的结合亲和力和更高的脑生物分布，从而更强地抑制 Aβ42 纤颤并更好地挽救 AD 模型小鼠的行为障碍。