Dataset Information

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 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.

SUBMITTER: Mead BP

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

REPOSITORIES: biostudies-literature

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

Mead Brian P BP Curley Colleen T CT Kim Namho N Negron Karina K Garrison William J WJ Song Ji J Rao Divya D Miller G Wilson GW Mandell James W JW Purow Benjamin W BW Suk Jung Soo JS Hanes Justin J Price Richard J RJ

Small (Weinheim an der Bergstrasse, Germany) 20191022 49

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 fi ...[more]

PMID: 31642183

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Project description:BackgroundFocused ultrasound (FUS) is an emerging technology, offering the capability of tuning and prescribing thermal and mechanical treatments within the brain. While early works in utilizing this technology have mainly focused on maximizing the delivery of therapeutics across the blood-brain barrier (BBB), the potential therapeutic impact of FUS-induced controlled thermal and mechanical stress to modulate anti-tumor immunity is becoming increasingly recognized.ObjectiveTo better understand the roles of FUS-mediated thermal and mechanical stress in promoting anti-tumor immunity in central nervous system tumors, we performed a comprehensive literature review on focused ultrasound-mediated immunomodulation and immunotherapy in brain tumors.MethodsFirst, we summarize the current clinical experience with immunotherapy. Then, we discuss the unique and distinct immunomodulatory effects of the FUS-mediated thermal and mechanical stress in the brain tumor-immune microenvironment. Finally, we highlight recent findings that indicate that its combination with immune adjuvants can promote robust responses in brain tumors.ResultsAlong with the rapid advancement of FUS technologies into recent clinical trials, this technology through mild-hyperthermia, thermal ablation, mechanical perturbation mediated by microbubbles, and histotripsy each inducing distinct vascular and immunological effects, is offering the unique opportunity to improve immunotherapeutic trafficking and convert immunologically "cold" tumors into immunologically "hot" ones that are prone to generate prolonged anti-tumor immune responses.ConclusionsWhile FUS technology is clearly accelerating concepts for new immunotherapeutic combinations, additional parallel efforts to detail rational therapeutic strategies supported by rigorous preclinical studies are still in need to leverage potential synergies of this technology with immune adjuvants. This work will accelerate the discovery and clinical implementation of new effective FUS immunotherapeutic combinations for brain tumor patients.

Dataset Information

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

Publications

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

Similar Datasets

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