Targeted Drug Delivery to Stroke via Chemotactic Recruitment of Nanoparticles Coated with Membrane of Engineered Neural Stem Cells.
CXCR4
glyburide
nanoparticles
neural stem cells
stroke
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
22
04
2019
revised:
17
06
2019
pubmed:
11
7
2019
medline:
21
10
2020
entrez:
11
7
2019
Statut:
ppublish
Résumé
Cell membrane coating has recently emerged as a promising biomimetic approach to engineering nanoparticles (NPs) for targeted drug delivery. However, simple cell membrane coating may not meet the need for efficient drug delivery to the brain. Here, a novel molecular engineering strategy to modify the surface of NPs with a cell membrane coating for enhanced brain penetration is reported. By using poly(lactic-co-glycolic) acid NPs as a model, it is shown that delivery of NPs to the ischemic brain is enhanced through surface coating with the membrane of neural stem cells (NSCs), and the delivery efficiency can be further increased using membrane isolated from NSCs engineered for overexpression of CXCR4. It is found that this enhancement is mediated by the chemotactic interaction of CXCR4 with SDF-1, which is enriched in the ischemic microenvironment. It is demonstrated that the resulting CXCR4-overexpressing membrane-coated NPs, termed CMNPs, significantly augment the efficacy of glyburide, an anti-edema agent, for stroke treatment. The study suggests a new approach to improving drug delivery to the ischemic brain and establishes a novel formulation of glyburide that can be potentially translated into clinical applications to improve management of human patients with stroke.
Identifiants
pubmed: 31290245
doi: 10.1002/smll.201902011
doi:
Substances chimiques
CXCL12 protein, human
0
CXCR4 protein, human
0
Chemokine CXCL12
0
Receptors, CXCR4
0
Glyburide
SX6K58TVWC
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1902011Subventions
Organisme : NINDS NIH HHS
ID : R01 NS095817
Pays : United States
Informations de copyright
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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