Journal
JOURNAL OF CONTROLLED RELEASE
Volume 217, Issue -, Pages 113-120Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2015.08.044
Keywords
Blood-brain barrier; Stem cells; MRI; High intensity focused ultrasound; Image guided drug delivery; HSP70
Funding
- NCI NIH HHS [R01 CA184091, R01 CA184091-01, P30 CA012197, R01 CA179072] Funding Source: Medline
- NIBIB NIH HHS [R01 EB009009] Funding Source: Medline
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The blood-brain barrier (BBB), comprised of brain endothelial cells with tight junctions (TJ) between them, regulates the extravasation of molecules and cells into and out of the central nervous system(CNS). Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of a broad range of brain disorders. Current strategies for BBB opening are invasive, not specific, and lack precise control over the site and timing of BBB opening, which may limit their clinical translation. In the present report, we describe a novel approach based on a combination of stem cell delivery, heat-inducible gene expression and mild heating with high-intensity focused ultrasound (HIFU) under MRI guidance to remotely permeabilize BBB. The permeabilization of the BBB will be controlled with, and limited to where selected proinflammatory factors will be secreted secondary to HIFU activation, which is in the vicinity of the engineered stem cells and consequently both the primary and secondary disease foci. This therapeutic platform thus represents a non-invasive way for BBB opening with unprecedented spatiotemporal precision, and if properly and specifically modified, can be clinically translated to facilitate delivery of different diagnostic and therapeutic agents which can have great impact in treatment of various disease processes in the central nervous system. (c) 2015 Elsevier B.V. All rights reserved.
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