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

被引：288

作者：

Hou, Ke ^{[1
,2
,3
]}

Zhao, Jing ^{[4
]}

Wang, Hui ^{[1
]}

Li, Bin ^{[1
,5
]}

Li, Kexin ^{[6
]}

Shi, Xinghua ^{[1
]}

Wan, Kaiwei ^{[1
]}

Ai, Jing ^{[6
]}

Lv, Jiawei ^{[1
]}

Wang, Dawei ^{[1
]}

Huang, Qunxing ^{[1
]}

Wang, Huayi ^{[1
]}

Cao, Qin ^{[7
,8
]}

Liu, Shaoqin ^{[4
]}

Tang, Zhiyong ^{[1
,3
]}

机构：

[1] Natl Ctr Nanosci & Technol, CAS Key Lab Nanosyst & Hierarch Fabricat, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China

[2] Peking Univ, Ctr Nanochem, Beijing 100871, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[4] Harbin Inst Technol, MOE Key Lab Microsyst & Microstruct Mfg, Sch Life Sci & Technol, Harbin 150001, Peoples R China

[5] Sun Yat Sen Univ, Sch Chem Engn & Technol, Zhuhai 519082, Peoples R China

[6] Harbin Med Univ, Dept Pharmacol, State Prov Key Labs Biomed Pharmaceut China, Coll Pharm, Harbin 150086, Peoples R China

[7] Univ Calif Los Angeles, Dept Chem & Biochem & Biol Chem, UCLA DOE Inst, Los Angeles, CA USA

[8] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90024 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PROTEIN FIBRILLATION; INHIBITION; FIBRILLOGENESIS; GLUTATHIONE; AGGREGATION; METABOLISM; CURVATURE; APPRAISAL; FORMS; DRUG;

D O I：

10.1038/s41467-020-18525-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 48 条

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