Detection of β-Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

被引:33
|
作者
Nasr, Seyedmehdi Hossaini [1 ]
Kouyoumdjian, Hovig [1 ,2 ]
Mallett, Christiane [3 ]
Ramadan, Sherif [1 ,4 ]
Zhu, David C. [3 ]
Shapiro, Erik M. [3 ,5 ,6 ]
Huang, Xuefei [1 ,5 ,6 ]
机构
[1] Michigan State Univ, Dept Chem, 578 S Shaw Lane, E Lansing, MI 48824 USA
[2] York Univ, Dept Chem, 4700 Keele St,Chem Bldg 350, Toronto, ON M3J 1P3 T, Canada
[3] Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA
[4] Benha Univ, Fac Sci, Chem Dept, Banha 13518, Qaliobiya, Egypt
[5] Michigan State Univ, Dept Biomed Engn, E Lansing, MI 48824 USA
[6] Michigan State Univ, Inst Quantitat Hlth Sci & Engn, E Lansing, MI 48824 USA
关键词
beta-amyloid; blood brain barrier; magnetic nanoparticles; magnetic resonance imaging; sialic acid; BLOOD-BRAIN-BARRIER; IRON-OXIDE NANOPARTICLES; TRANSGENIC MICE; INDUCED TOXICITY; DRUG-DELIVERY; PLAQUES; PROTEIN; ATTENUATION; PEPTIDE; MECHANISM;
D O I
10.1002/smll.201701828
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The accumulation and formation of beta-amyloid (A beta) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with A beta highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for A beta binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSA(x)-Sia) to overcome the challenges in A beta imaging in vivo. The NP-BSA(x)-Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP-BSA(x)-Sia binds with A beta in a sialic acid dependent manner with high selectivities toward A beta deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect A beta in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T-2(star)-weighted MRI shows that A beta plaques in mouse brains can be detected as aided by NP-BSA(x)-Sia, which is confirmed by histological analysis. Thus, NP-BSA(x)-Sia is a promising new tool for noninvasive in vivo detection of A beta plaques.
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页数:10
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