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Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro

Gromnicova, Radka; Davies, Heather A.; Sreekanthreddy, Pedagannganagari; Romero, Ignacio A.; Lund, Torben; Roitt, Ivan M.; Phillips, James B. and Male, David K. (2013). Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro. PLoS ONE, 8(12), article no. e81043.

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URL: http://www.plosone.org/article/info%3Adoi%2F10.137...
DOI (Digital Object Identifier) Link: https://doi.org/10.1371/journal.pone.0081043
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Abstract

The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

Item Type: Journal Item
Copyright Holders: 2013 Gromnicova et al.
ISSN: 1932-6203
Project Funding Details:
Funded Project NameProject IDFunding Body
The response of human brain endothelium and astrocytes to vasoactive mediatorsNot SetMigraine Trust
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Innovation, Knowledge & Development research centre (IKD)
Item ID: 39119
Depositing User: David Male
Date Deposited: 11 Dec 2013 09:43
Last Modified: 19 Nov 2016 06:40
URI: http://oro.open.ac.uk/id/eprint/39119
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