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

Ke Hou, Jing 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 () and Zhiyong Tang ()
Additional contact information
Ke Hou: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Jing Zhao: MOE Key Laboratory of Micro-systems and Micro-structures Manufacturing, School of Life Science and Technology, Harbin Institute of Technology
Hui Wang: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Bin Li: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Kexin Li: the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, College of Pharmacy of Harbin Medical University
Xinghua Shi: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Kaiwei Wan: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Jing Ai: the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, College of Pharmacy of Harbin Medical University
Jiawei Lv: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Dawei Wang: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Qunxing Huang: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Huayi Wang: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology
Qin Cao: UCLA-DOE Institute and Howard Hughes Medical Institute, UCLA
Shaoqin Liu: MOE Key Laboratory of Micro-systems and Micro-structures Manufacturing, School of Life Science and Technology, Harbin Institute of Technology
Zhiyong Tang: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18525-2

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