Enhanced delivery of AAV-like nanoparticles after blood-brain barrier disruption in a mouse model
| Autor: | Katherine W. Ferrara, Jai Woong Seo, Sarah Tam, Josquin Foiret, Hua Zhang, Hamilton Kakwere, Lisa M. Mahakian |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.diagnostic_test Chemistry Nanoparticle Transfection Blood–brain barrier Focused ultrasound 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Positron emission tomography In vivo Ultrasound imaging medicine Blood-brain barrier disruption 030217 neurology & neurosurgery Biomedical engineering |
| Zdroj: | 2019 IEEE International Ultrasonics Symposium (IUS). |
| DOI: | 10.1109/ultsym.2019.8925683 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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