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Nanomedicine. 2016 Oct;12(7):1833-1842. doi: 10.1016/j.nano.2016.03.005. Epub 2016 Mar 30.

Targeted drug delivery to ischemic stroke via chlorotoxin-anchored, lexiscan-loaded nanoparticles.

Author information

1
Department of Neurosurgery, Yale University, New Haven, CT, USA; School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
2
Department of Neurosurgery, Yale University, New Haven, CT, USA; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
3
Department of Neurosurgery, Yale University, New Haven, CT, USA.
4
Department of Neurosurgery, Yale University, New Haven, CT, USA; The laboratory of Cell Biology and Translational Medicine, Xi'an Medical University, Xi'an, China.
5
Department of Neurology, Yale University, New Haven, CT, USA.
6
Division of Biostatistics, School of Public Health, Yale University, New Haven, CT, USA.
7
Department of Neurosurgery, Yale University, New Haven, CT, USA; Department of Neurology, Yale University, New Haven, CT, USA.
8
Department of Neurosurgery, Yale University, New Haven, CT, USA; Department of Biomedical Engineering, Yale University, New Haven, CT, USA. Electronic address: jiangbing.zhou@yale.edu.

Abstract

Ischemic stroke is a leading cause of disability and death worldwide. Current drug treatment for stroke remains inadequate due to the existence of the blood-brain barrier. We proposed an innovative nanotechnology-based autocatalytic targeting approach, in which the blood-brain barrier modulator lexiscan is encapsulated in nanoparticles to enhance blood-brain barrier permeability and autocatalytically augment the brain stroke-targeting delivery efficiency of chlorotoxin-anchored nanoparticles. The nanoparticles efficiently and specifically accumulated in the brain ischemic microenvironment and the targeting efficiency autocatalytically increased with subsequent administrations. When Nogo-66 receptor antagonist peptide NEP1-40, a potential therapeutic agent for ischemic stroke, was loaded, nanoparticles significantly reduced infarct volumes and enhanced survival. Our findings suggest that the autocatalytic targeting approach is a promising strategy for drug delivery to the ischemic microenvironment inside the brain. Nanoparticles developed in this study may serve as a new approach for the clinical management of stroke.

KEYWORDS:

Autocatalytic targeting; Blood–brain barrier; Chlorotoxin; Lexiscan; Nanoparticles; Stroke

PMID:
27039220
PMCID:
PMC5045320
DOI:
10.1016/j.nano.2016.03.005
[Indexed for MEDLINE]
Free PMC Article

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