L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles
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Supporting information
Accepted version
Author(s)
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.
Date Issued
2019-01
Date Acceptance
2018-08-19
Citation
Nanomedicine: Nanotechnology, Biology and Medicine, 2019, 15 (1), pp.1-11
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
Commission of the European Communities
Commission of the European Communities
Commission of the European Communities
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30189294
PII: S1549-9634(18)30515-X
Grant Number
ERC-2010-StG-20091028
PIEF-GA-2013-627049
PIIF-GA-2013-624475
Subjects
Blood–brain barrier
Brain targeting
Gold nanoparticles
L-DOPA
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-09-03