Journal
SMALL
Volume 14, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201701828
Keywords
beta-amyloid; blood brain barrier; magnetic nanoparticles; magnetic resonance imaging; sialic acid
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Funding
- National Institute of General Medical Sciences, the NIH [R01GM072667]
- Michigan State University
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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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