TY - JOUR
T1 - Remote spatiotemporally controlled and biologically selective permeabilization of blood-brain barrier
AU - Xiong, Xiaobing
AU - Sun, Yao
AU - Sattiraju, Anirudh
AU - Jung, Youngkyoo
AU - Mintz, Akiva
AU - Hayasaka, Satoru
AU - Li, King C.P.
PY - 2015/11/10
Y1 - 2015/11/10
N2 - 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 pro-inflammatory 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.
AB - 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 pro-inflammatory 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.
KW - Blood-brain barrier
KW - High intensity focused ultrasound
KW - HSP70
KW - Image guided drug delivery
KW - MRI
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=84940978184&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940978184&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2015.08.044
DO - 10.1016/j.jconrel.2015.08.044
M3 - Article
C2 - 26334482
AN - SCOPUS:84940978184
VL - 217
SP - 113
EP - 120
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
M1 - 7824
ER -