TY - GEN
T1 - Enhanced delivery of AAV-like nanoparticles after blood-brain barrier disruption in a mouse model
AU - Foiret, Josquin
AU - Seo, Jai Woong
AU - Zhang, Hua
AU - Kakwere, Hamilton
AU - Mahakian, Lisa M.
AU - Tam, Sarah
AU - Ferrara, Katherine W
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - blood brain barrier opening
KW - focused ultrasound
KW - nanoparticle
KW - passive acoustic mapping
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85077519164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077519164&partnerID=8YFLogxK
U2 - 10.1109/ULTSYM.2019.8925683
DO - 10.1109/ULTSYM.2019.8925683
M3 - Conference contribution
AN - SCOPUS:85077519164
T3 - IEEE International Ultrasonics Symposium, IUS
SP - 884
EP - 887
BT - 2019 IEEE International Ultrasonics Symposium, IUS 2019
PB - IEEE Computer Society
T2 - 2019 IEEE International Ultrasonics Symposium, IUS 2019
Y2 - 6 October 2019 through 9 October 2019
ER -