Enhanced delivery of AAV-like nanoparticles after blood-brain barrier disruption in a mouse model

Josquin Foiret, Jai Woong Seo, Hua Zhang, Hamilton Kakwere, Lisa M. Mahakian, Sarah Tam, Katherine W Ferrara

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Focused ultrasound (FUS) to open the blood brain barrier (BBB) is under evaluation for the delivery of therapeutic agents to the brain. Regarding delivery of genes through the BBB, adeno-associated viruses (AAVs) have generated interest due to their ability to specifically and efficiently transfect the brain, which was recently demonstrated in mouse models. In this work, we investigated the use of 1.5 MHz FUS-mediated BBB opening in a mouse model after systemic injection of AAV-like polymer nanoparticles designed to have a 20-nm size and a targeting peptide similar to AAV-PHP.eB. Radiolabeling of the nanoparticles allowed in vivo tracking of the accumulation in the brain following the FUS treatment with positron emission tomography imaging (PET). Significant accumulation was measured in the treated hemisphere with a 1.8-fold enhancement compared to the contra-lateral hemisphere. Our experimental setup optimized for rodents (Verasonics) enables ultrasound imaging, precise targeting with electronic steering, and monitoring of the cavitation activity during the FUS treatment using passive acoustic mapping.

Original languageEnglish (US)
Title of host publication2019 IEEE International Ultrasonics Symposium, IUS 2019
PublisherIEEE Computer Society
Pages884-887
Number of pages4
ISBN (Electronic)9781728145969
DOIs
StatePublished - Oct 2019
Externally publishedYes
Event2019 IEEE International Ultrasonics Symposium, IUS 2019 - Glasgow, United Kingdom
Duration: Oct 6 2019Oct 9 2019

Publication series

NameIEEE International Ultrasonics Symposium, IUS
Volume2019-October
ISSN (Print)1948-5719
ISSN (Electronic)1948-5727

Conference

Conference2019 IEEE International Ultrasonics Symposium, IUS 2019
CountryUnited Kingdom
CityGlasgow
Period10/6/1910/9/19

Keywords

  • blood brain barrier opening
  • focused ultrasound
  • nanoparticle
  • passive acoustic mapping
  • positron emission tomography

ASJC Scopus subject areas

  • Acoustics and Ultrasonics

Fingerprint Dive into the research topics of 'Enhanced delivery of AAV-like nanoparticles after blood-brain barrier disruption in a mouse model'. Together they form a unique fingerprint.

  • Cite this

    Foiret, J., Seo, J. W., Zhang, H., Kakwere, H., Mahakian, L. M., Tam, S., & Ferrara, K. W. (2019). Enhanced delivery of AAV-like nanoparticles after blood-brain barrier disruption in a mouse model. In 2019 IEEE International Ultrasonics Symposium, IUS 2019 (pp. 884-887). [8925683] (IEEE International Ultrasonics Symposium, IUS; Vol. 2019-October). IEEE Computer Society. https://doi.org/10.1109/ULTSYM.2019.8925683