Remote spatiotemporally controlled and biologically selective permeabilization of blood-brain barrier

Xiaobing Xiong, Yao Sun, Anirudh Sattiraju, Youngkyoo Jung, Akiva Mintz, Satoru Hayasaka, King C.P. Li

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number7824
Pages (from-to)113-120
Number of pages8
JournalJournal of Controlled Release
Volume217
DOIs
StatePublished - Nov 10 2015
Externally publishedYes

Keywords

  • Blood-brain barrier
  • High intensity focused ultrasound
  • HSP70
  • Image guided drug delivery
  • MRI
  • Stem cells

ASJC Scopus subject areas

  • Pharmaceutical Science

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