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Focused Ultrasound Preconditioning for Augmented Nanoparticle Penetration and Efficacy in the Central Nervous System
Author(s) -
Mead Brian P.,
Curley Colleen T.,
Kim Namho,
Negron Karina,
Garrison William J.,
Song Ji,
Rao Divya,
Miller G. Wilson,
Mandell James W.,
Purow Benjamin W.,
Suk Jung Soo,
Hanes Justin,
Price Richard J.
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201903460
Subject(s) - transfection , central nervous system , gene delivery , magnetic resonance imaging , parenchyma , ultrasound , nanoparticle , penetration (warfare) , biomedical engineering , blood–brain barrier , materials science , biophysics , nanotechnology , medicine , chemistry , neuroscience , pathology , biology , gene , biochemistry , radiology , operations research , engineering
Microbubble activation with focused ultrasound (FUS) facilitates the noninvasive and spatially‐targeted delivery of systemically administered therapeutics across the blood–brain barrier (BBB). FUS also augments the penetration of nanoscale therapeutics through brain tissue; however, this secondary effect has not been leveraged. Here, 1 MHz FUS sequences that increase the volume of transfected brain tissue after convection‐enhanced delivery of gene‐vector “brain‐penetrating” nanoparticles were first identified. Next, FUS preconditioning is applied prior to trans‐BBB nanoparticle delivery, yielding up to a fivefold increase in subsequent transgene expression. Magnetic resonance imaging (MRI) analyses of tissue temperature and K trans confirm that augmented transfection occurs through modulation of parenchymal tissue with FUS. FUS preconditioning represents a simple and effective strategy for markedly improving the efficacy of gene vector nanoparticles in the central nervous system.