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GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the Combination Therapy of Alzheimer's Disease 期刊论文

编号：

9e67d3c4-1955-4d3d-b45f-be0731baeaad
作者：

Huang, Meng^[1];Hu, Meng^[1];Song, Qingxiang^[1];Song, Huahua^[1];Huang, Jialin^[1];Gu, Xiao^[1];Wang, Xiaolin^[1];Chen, Jun(陈钧)^[2]Kang, Ting^[2];Feng, Xingye^[2];Jiang, Di^[2];Zheng, Gang^[3,4];Chen, Hongzhuan^[1];Gao, Xiaoling^[1];
语种：

English
期刊：

ACS NANO ISSN：1936-0851 2015 年 9 卷 11 期 (10801 - 10816) ; NOV
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关键词：

reconstituted high-density lipoprotein nanoplatform Alzheimer's disease amyloid-beta combination therapy GM1 ganglioside intranasal administration
摘要：

Alzheimer's disease (AD) exerts a heavy health burden for modern society and has a complicated pathological background. The accumulation of extracellular beta-amyloid (A beta) is crucial in AD pathogenesis, and A beta-initiated secondary pathological processes could independently lead to neuronal degeneration and pathogenesis in AD. Thus, the development of combination therapeutics that can not only accelerate A beta clearance but also simultaneously protect neurons or inhibit other subsequent pathological cascade represents a promising strategy for AD intervention. Here, we designed a nanostructure, monosialotetrahexosylganglioside (GM1)-modified reconstituted high density lipoprotein (GM1-rHDL), that possesses antibody-like high binding affinity to A beta, facilitates A beta degradation by microglia, and A beta efflux across the blood brain barrier (BBB), displays high brain biodistribution efficiency following intranasal administration, and simultaneously allows the efficient loading of a neuroprotective peptide, NAP, as a nanoparticulate drug delivery system for the combination therapy of AD. The resulting multifunctional nanostructure, alpha NAP-GM1-rHDL, was found to be able to protect neurons from A beta(1-42) oligomer/glutamic acid-induced cell toxicity better than GM1-rHDL in vitro and reduced A beta deposition, ameliorated neurologic changes, and rescued memory loss more efficiently than both alpha NAP solution and GM1-rHDL in AD model mice following intranasal administration with no observable cytotoxicity noted. Taken together, this work presents direct experimental evidence of the rational design of a biomimetic nanostructure to serve as a safe and efficient multifunctional nanoplatform for the combination therapy of AD.
推荐引用方式
GB/T 7714：

Huang Meng,Hu Meng,Song Qingxiang, et al. GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the Combination Therapy of Alzheimer's Disease [J].ACS NANO,2015,9(11):10801-10816.
APA：

Huang Meng,Hu Meng,Song Qingxiang,Song Huahua,&Gao Xiaoling.(2015).GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the Combination Therapy of Alzheimer's Disease .ACS NANO,9(11):10801-10816.
MLA：

Huang Meng, et al. "GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the Combination Therapy of Alzheimer's Disease" .ACS NANO 9,11(2015):10801-10816.

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