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PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering A beta generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice
Huang, Na1,2; Lu, Shuai1; Liu, Xiao-Ge1,3; Zhu, Jie1; Wang, Yu-Jiong2; Liu, Rui-Tian1
2017-10-06
发表期刊ONCOTARGET
ISSN1949-2553
卷号8期号:46页码:81001-81013
摘要

Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid beta (A beta) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with A beta generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of A beta, reactive oxygen species (ROS), TNF-alpha and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.

关键词Alzheimer's Disease Nanoparticles Beta-amyloid Curcumin Peptide
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.18632/oncotarget.20944
收录类别SCI
语种英语
关键词[WOS]Blood-brain-barrier ; Protein-cleaving Enzyme ; Drug-delivery ; Neurodegenerative Diseases ; Mouse Model ; Bace1 ; Secretase ; Encapsulation ; Neurogenesis ; Glioblastoma
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
项目资助者National Natural Science Foundation of China(31401158) ; National Science and Technology Major Projects of New Drugs(2014ZX09102045-006) ; State Key Laboratory of Biochemical Engineering(2015KF-02)
WOS记录号WOS:000412465700078
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/23276
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Ningxia Univ, Key Lab Minist Educ Protect & Utilizat Special Bi, Yinchuan 750021, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Huang, Na,Lu, Shuai,Liu, Xiao-Ge,et al. PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering A beta generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice[J]. ONCOTARGET,2017,8(46):81001-81013.
APA Huang, Na,Lu, Shuai,Liu, Xiao-Ge,Zhu, Jie,Wang, Yu-Jiong,&Liu, Rui-Tian.(2017).PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering A beta generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice.ONCOTARGET,8(46),81001-81013.
MLA Huang, Na,et al."PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering A beta generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice".ONCOTARGET 8.46(2017):81001-81013.
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