Curley, Colleen T.Mead, Brian P.Negron, KarinaKim, NamhoGarrison, William J.Miller, G. WilsonKingsmore, Kathryn M.Thim, E. AndrewSong, JiMunson, Jennifer M.Klibanov, Alexander L.Suk, Jung SooHanes, JustinPrice, Richard J.2020-09-092020-09-092020-042375-2548eaay1344http://hdl.handle.net/10919/99934The 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.application/pdfenCreative Commons Attribution-NonCommercial 4.0 InternationalArticle - Refereedhttps://doi.org/10.1126/sciadv.aay134461832494662