期刊
ACTA BIOMATERIALIA
卷 25, 期 -, 页码 172-183出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.06.035
关键词
Selenium nanoparticles; B6 peptide; Blood-brain barrier; Fibril; Oligomer
资金
- National Natural Science Foundation of China [21171070, 21371075]
- National Natural Science Foundation of Guangdong Province [2014A030311025]
- Chinese Postdoctoral Science Foundation
The blood-brain barrier (BBB) is a formidable gatekeeper toward exogenous substances, playing an important role in brain homeostasis and maintaining a healthy microenvironment for complex neuronal activities. However, it also greatly hinders drug permeability into the brain and limits the management of brain diseases. The development of new drugs that show improved transport across the BBB represents a promising strategy for Alzheimer's disease (AD) intervention. Whereas, previous study of receptor-mediated endogenous BBB transport systems has focused on a strategy of using transferrin to facilitate brain drug delivery system, a system that still suffers from limitations including synthesis procedure, stability and immunological response. In the present study, we synthetised sialic acid (SA)-modified selenium (Se) nanoparticles conjugated with an alternative peptide-B6 peptide (B6-SA-SeNP5, a synthetic selenoprotein analogue), which shows high permeability across the BBB and has the potential to serve as a novel nanomedicine for disease modification in AD. Laser-scanning confocal microscopy, flow cytometry analysis and inductively coupled plasma-atomic emission spectroscopy ICP-AES revealed high cellular uptake of B6-SA-SeNP5 by cerebral endothelial cells (bEnd3). The transport efficiency of B6-SA-SeNP5 was evaluated in a Transwell experiment based on in vitro BBB model. It provided direct evidence for B6-SA-SeNP5 crossing the BBB and being absorbed by PC12 cells. Moreover, inhibitory effects of B6-SA-SeNPs on amyloid-beta peptide (A beta) fibrillation could be demonstrated in PC12 cells and bEnd3 cells. B6-SA-SeNP5 could not only effectively inhibit A beta aggregation but could disaggregate preformed A beta fibrils into non-toxic amorphous oligomers. These results suggested that B6-SA-SeNP5 may provide a promising platform, particularly for the application of nanoparticles in the treatment of brain diseases. Statement of Significance Alzheimer's disease (AD) is the world's most common form of dementia characterized by intracellular neurofibrillary tangles in the brain. Over the past decades, the blood-brain barrier (BBB) limits access of therapeutic or diagnostic agents into the brain, which greatly hinders the development of new drugs for treating AD. In this work, we evaluated the efficiency of B6-SA-SeNP5 across BBB and investigated the interactions between B6-SA-SeNP5 and amyloid-beta peptide (A beta). We confirm that B6-SA-SeNP5 could provide a promising platform because of its high brain delivery efficiency, anti-amyloid properties and anti-oxidant properties, which may serve as a novel nanomedicine for the application in the treatment of brain diseases. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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