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

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dc.contributor.authorCurley, Colleen T.en
dc.contributor.authorMead, Brian P.en
dc.contributor.authorNegron, Karinaen
dc.contributor.authorKim, Namhoen
dc.contributor.authorGarrison, William J.en
dc.contributor.authorMiller, G. Wilsonen
dc.contributor.authorKingsmore, Kathryn M.en
dc.contributor.authorThim, E. Andrewen
dc.contributor.authorSong, Jien
dc.contributor.authorMunson, Jennifer M.en
dc.contributor.authorKlibanov, Alexander L.en
dc.contributor.authorSuk, Jung Sooen
dc.contributor.authorHanes, Justinen
dc.contributor.authorPrice, Richard J.en
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessioned2020-09-09T13:28:09Zen
dc.date.available2020-09-09T13:28:09Zen
dc.date.issued2020-04en
dc.description.abstractThe 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 extra-cellular 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 similar to 70 degrees to 80 degrees. 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.en
dc.description.notesR.J.P., J.H., and J.S.S. were supported by NIH R01CA164789, R01CA197111, R01CA204968, and R01EB020147. J.M.M. was supported by NIH R372222563. A.L. K. was supported by NIH R01EB023055. K.M.K. was supported by an NSFGRF.en
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01EB023055, R01CA164789, R01CA197111, R01CA204968, R01EB020147, R372222563]; NSFGRFNational Science Foundation (NSF)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1126/sciadv.aay1344en
dc.identifier.issn2375-2548en
dc.identifier.issue18en
dc.identifier.othereaay1344en
dc.identifier.pmid32494662en
dc.identifier.urihttp://hdl.handle.net/10919/99934en
dc.identifier.volume6en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.titleAugmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfectionen
dc.title.serialScience Advancesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Scholarly Works, Biomedical Engineering and Mechanics
Destination Area: Adaptive Brain and Behavior (ABB)