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

Colleen T. Curley | Zendy; Brian Mead | Zendy; Kariegrón | Zendy; Namho Kim | Zendy; William J. Garrison | Zendy; G. Wilson Miller | Zendy; Kathryn M. Kingsmore | Zendy; E. Andrew Thim | Zendy; Ji Song | Zendy; Jennifer M. Munson | Zendy; Alexander L. Klibanov | Zendy; Jung Soo Suk | Zendy; Justin Hanes | Zendy; Richard J. Price | Zendy

Open Access

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

Author(s) -

Colleen T. Curley,

Brian Mead,

Kariegrón,

Namho Kim,

William J. Garrison,

G. Wilson Miller,

Kathryn M. Kingsmore,

E. Andrew Thim,

Ji Song,

Jennifer M. Munson,

Alexander L. Klibanov,

Jung Soo Suk,

Justin Hanes,

Richard J. Price

Publication year - 2020

Publication title -

science advances

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.928

H-Index - 146

ISSN - 2375-2548

DOI - 10.1126/sciadv.aay1344

Subject(s) - nanocarriers , transfection , ultrasound , focused ultrasound , gene delivery , nanoparticle , brain tumor , biomedical engineering , medicine , cancer research , materials science , nanotechnology , gene , chemistry , pathology , radiology , biochemistry

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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