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

Preventing aggregation of amyloid beta (A beta) peptides is a promising strategy for the treatment of Alzheimer's disease (AD), and gold nanoparticles have previously been explored as a potential anti-A beta 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 A beta 42 and cross the blood-brain barrier (BBB) following intravenous administration without noticeable toxicity. D3.3 possesses a larger binding affinity to A beta 42 and higher brain biodistribution compared with its enantiomer L3.3, giving rise to stronger inhibition of A beta 42 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. Nanoparticles are being explored as a potential method to target A beta aggregation in Alzheimer's disease. Here, the authors develop gold nanoparticles that were capped with chiral L or D-glutathione which has been shown to improve BBB permeability and demonstrate their ability to improve cognitive function in a mouse model of AD.