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L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles

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Title: L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles
Authors: Gonzalez-Carter, DA
Ong, ZY
McGilvery, CM
Dunlop, IE
Dexter, DT
Porter, AE
Item Type: Journal Article
Abstract: The blood-brain barrier (BBB) is a protective endothelial barrier lining the brain microvasculature which prevents brain delivery of therapies against brain diseases. Hence, there is an urgent need to develop vehicles which efficiently penetrate the BBB to deliver therapies into the brain. The drug L-DOPA efficiently and specifically crosses the BBB via the large neutral amino acid transporter (LAT)-1 protein to enter the brain. Thus, we synthesized L-DOPA-functionalized multi-branched nanoflower-like gold nanoparticles (L-DOPA-AuNFs) using a seed-mediated method involving catechols as a direct reducing-cum-capping agent, and examined their ability to cross the BBB to act as brain-penetrating nanovehicles. We show that L-DOPA-AuNFs efficiently penetrate the BBB compared to similarly sized and shaped AuNFs functionalized with a non-targeting ligand. Furthermore, we show that L-DOPA-AuNFs are efficiently internalized by brain macrophages without inducing inflammation. These results demonstrate the application of L-DOPA-AuNFs as a non-inflammatory BBB-penetrating nanovehicle to efficiently deliver therapies into the brain.
Issue Date: 3-Sep-2018
Date of Acceptance: 19-Aug-2018
URI: http://hdl.handle.net/10044/1/63483
DOI: https://dx.doi.org/10.1016/j.nano.2018.08.011
ISSN: 1549-9634
Publisher: Elsevier
Start Page: 1
End Page: 11
Journal / Book Title: Nanomedicine: Nanotechnology, Biology and Medicine
Volume: 15
Issue: 1
Copyright Statement: © 2018 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Commission of the European Communities
Commission of the European Communities
Commission of the European Communities
Funder's Grant Number: ERC-2010-StG-20091028
PIEF-GA-2013-627049
PIIF-GA-2013-624475
Keywords: Blood–brain barrier
Brain targeting
Gold nanoparticles
L-DOPA
10 Technology
03 Chemical Sciences
06 Biological Sciences
Nanoscience & Nanotechnology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-09-03
Appears in Collections:Materials
Department of Medicine (up to 2019)
Faculty of Natural Sciences
Faculty of Engineering