한빛사논문
- 조회1,454
Colleen T. Curley1,*, Brian P. Mead1,*, Karina Negron2,3, Namho Kim2,4, William J. Garrison1, G. Wilson Miller1,5, Kathryn M. Kingsmore1, E. Andrew Thim1, Ji Song1, Jennifer M. Munson6, Alexander L. Klibanov1,7, Jung Soo Suk2,3,†, Justin Hanes2,3,4,† and Richard J. Price1,5,†
1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
2Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
3Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
5Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA.
6Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
7Cardiovascular Division, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
†Corresponding author.
*These authors contributed equally to this work.
Abstract
The delivery of systemically administered gene therapies to brain tumors is exceptionally difficult because of the blood-brain barrier (BBB) and blood-tumor barrier (BTB). In addition, the adhesive and nanoporous tumor extracellular matrix hinders therapeutic dispersion. We first developed the use of magnetic resonance image (MRI)–guided focused ultrasound (FUS) and microbubbles as a platform approach for transfecting brain tumors by targeting the delivery of systemically administered “brain-penetrating” nanoparticle (BPN) gene vectors across the BTB/BBB. Next, using an MRI-based transport analysis, we determined that after FUS-mediated BTB/BBB opening, mean interstitial flow velocity magnitude doubled, with “per voxel” flow directions changing by an average of ~70° to 80°. Last, we observed that FUS-mediated BTB/BBB opening increased the dispersion of directly injected BPNs through tumor tissue by >100%. We conclude that FUS-mediated BTB/BBB opening yields markedly augmented interstitial tumor flow that, in turn, plays a critical role in enhancing BPN transport through tumor tissue.
논문정보
- Research article
- 2020년 05월 (BRIC 등록일 2020-05-19)
- 국외 연구진
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