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Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease
Small ( IF 13.0 ) Pub Date : 2017-11-14 , DOI: 10.1002/smll.201701828
Seyedmehdi Hossaini Nasr 1 , Hovig Kouyoumdjian 1, 2 , Christiane Mallett 3 , Sherif Ramadan 1, 4 , David C Zhu 3 , Erik M Shapiro 3, 5 , Xuefei Huang 1, 5
Affiliation  

The accumulation and formation of β‐amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ 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 Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP‐BSAx‐Sia) to overcome the challenges in Aβ imaging in vivo. The NP‐BSAx‐Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP‐BSAx‐Sia binds with Aβ in a sialic acid dependent manner with high selectivities toward Aβ deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβ in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T2*‐weighted MRI shows that Aβ plaques in mouse brains can be detected as aided by NP‐BSAx‐Sia, which is confirmed by histological analysis. Thus, NP‐BSAx‐Sia is a promising new tool for noninvasive in vivo detection of Aβ plaques.

中文翻译:


唾液酸包被的牛血清白蛋白磁性纳米颗粒在阿尔茨海默病小鼠模型中检测 β-淀粉样蛋白



大脑中β-淀粉样蛋白(Aβ)斑块的积累和形成是阿尔茨海默病(AD)的独特病理标志。设计能够高度选择性地与 Aβ 结合的纳米颗粒 (NP) 造影剂可能有助于 AD 的早期检测。然而,一个重要的障碍是血脑屏障(BBB),它可以阻止 NP 进入大脑进行 Aβ 结合。在这项工作中,牛血清白蛋白(BSA)包被的纳米粒子用唾液酸(NP-BSA x -Sia)装饰,以克服体内 Aβ 成像的挑战。 NP-BSA x ‐Sia 具有高磁弛豫率的生物相容性,表明它们是适合磁共振成像 (MRI) 的造影剂。 NP-BSA x- Sia 以唾液酸依赖性方式与 Aβ 结合,对沉积在大脑上的 Aβ 具有高选择性,并在体外模型中穿过 BBB。通过 MRI 评估这些 NP 在人类 AD 转基因小鼠体内检测 Aβ 的能力,无需同时注射甘露醇以增加 BBB 通透性。 T 2 *加权MRI显示,在NP-BSA x ‐Sia的辅助下,可以检测到小鼠大脑中的Aβ斑块,并经组织学分析证实。因此,NP-BSA x ‐Sia 是一种有前途的无创体内 Aβ 斑块检测新工具。
更新日期:2017-11-14
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