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Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection

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 o...

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Autores principales: Curley, Colleen T., Mead, Brian P., Negron, Karina, Kim, Namho, Garrison, William J., Miller, G. Wilson, Kingsmore, Kathryn M., Thim, E. Andrew, Song, Ji, Munson, Jennifer M., Klibanov, Alexander L., Suk, Jung Soo, Hanes, Justin, Price, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195188/
https://www.ncbi.nlm.nih.gov/pubmed/32494662
http://dx.doi.org/10.1126/sciadv.aay1344
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author Curley, Colleen T.
Mead, Brian P.
Negron, Karina
Kim, Namho
Garrison, William J.
Miller, G. Wilson
Kingsmore, Kathryn M.
Thim, E. Andrew
Song, Ji
Munson, Jennifer M.
Klibanov, Alexander L.
Suk, Jung Soo
Hanes, Justin
Price, Richard J.
author_facet Curley, Colleen T.
Mead, Brian P.
Negron, Karina
Kim, Namho
Garrison, William J.
Miller, G. Wilson
Kingsmore, Kathryn M.
Thim, E. Andrew
Song, Ji
Munson, Jennifer M.
Klibanov, Alexander L.
Suk, Jung Soo
Hanes, Justin
Price, Richard J.
author_sort Curley, Colleen T.
collection PubMed
description 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.
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spelling pubmed-71951882020-06-02 Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection Curley, Colleen T. Mead, Brian P. Negron, Karina Kim, Namho Garrison, William J. Miller, G. Wilson Kingsmore, Kathryn M. Thim, E. Andrew Song, Ji Munson, Jennifer M. Klibanov, Alexander L. Suk, Jung Soo Hanes, Justin Price, Richard J. Sci Adv Research Articles 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. American Association for the Advancement of Science 2020-05-01 /pmc/articles/PMC7195188/ /pubmed/32494662 http://dx.doi.org/10.1126/sciadv.aay1344 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Curley, Colleen T.
Mead, Brian P.
Negron, Karina
Kim, Namho
Garrison, William J.
Miller, G. Wilson
Kingsmore, Kathryn M.
Thim, E. Andrew
Song, Ji
Munson, Jennifer M.
Klibanov, Alexander L.
Suk, Jung Soo
Hanes, Justin
Price, Richard J.
Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
title Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
title_full Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
title_fullStr Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
title_full_unstemmed Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
title_short Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
title_sort augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195188/
https://www.ncbi.nlm.nih.gov/pubmed/32494662
http://dx.doi.org/10.1126/sciadv.aay1344
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