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

Publication date: October 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine, Volume 12, Issue 7 Author(s): Liang Han, Qiang Cai, Daofeng Tian, Derek K. Kong, Xingchun Gou, Zeming Chen, Stephen M. Strittmatter, Zuoheng Wang, Kevin N. Sheth, Jiangbing Zhou 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. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research