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

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 K_trans confirm that augmented transfection occurs throu

SUBMITTER: Mead BP 

PROVIDER: S-EPMC7084172 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature