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

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• 作者：Liang Han ; PhD^a ; ^b ; Qiang Cai ; MD^a ; ^c ; Daofeng Tian ; MD^a ; ^c ; Derek K. Kong ; MS^a ; Xingchun Gou ; PhD^a ; ^d ; Zeming Chen ; BS^a ; Stephen M. Strittmatter ; MD ; PhD^e ; Zuoheng Wang ; PhD^f ; Kevin N. Sheth ; MD^a ; ^e ; Jiangbing Zhou ; PhD^a ; ^g ; ^{jiangbing.zhou@yale.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Stroke ; Blood&ndash ; brain barrier ; Autocatalytic targeting ; Lexiscan ; Chlorotoxin ; Nanoparticles
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：7
• 页码：1833-1842
• 全文大小：1029 K

文摘

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.