Focused Ultrasound Preconditioning for Augmented Nanoparticle Penetration and Efficacy in the Central Nervous System

Brian P. Mead, Colleen T. Curley, Namho Kim, Karina Negron, William J. Garrison, Ji Song, Divya Rao, G. Wilson Miller, James W. Mandell, Benjamin W. Purow, Jung Soo Suk, Justin Hanes, Richard J. Price

Research output: Contribution to journalArticle

Abstract

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 Ktrans 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.

Original languageEnglish (US)
Article number1903460
JournalSmall
Volume15
Issue number49
DOIs
StatePublished - Dec 1 2019

Keywords

  • focused ultrasound
  • microbubbles
  • nanoparticles
  • nonviral gene delivery

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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    Mead, B. P., Curley, C. T., Kim, N., Negron, K., Garrison, W. J., Song, J., Rao, D., Miller, G. W., Mandell, J. W., Purow, B. W., Suk, J. S., Hanes, J., & Price, R. J. (2019). Focused Ultrasound Preconditioning for Augmented Nanoparticle Penetration and Efficacy in the Central Nervous System. Small, 15(49), [1903460]. https://doi.org/10.1002/smll.201903460