Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain
Open accessAbstract
Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability. In this study, FUS/microbubble-assisted BBB opening was investigated for the intravenous delivery of mRNA-LNP to the brain. The intensity of FUS irradiation was optimized to 1.5 kW/cm 2, at which BBB opening occurred efficiently without hemorrhage or edema. Exogenous protein (luciferase) expression by mRNA-LNP, specifically at the FUS-irradiated side of the brain, occurred only when FUS and microbubbles were applied. This exogenous protein expression was faster but shorter than that of plasmid DNA delivery. Furthermore, foreign protein expression was observed in the microglia, along with CD31-positive endothelial cells, whereas no expression was observed in astrocytes or neurons. These results support the addition of mRNA-LNP to the lineup of nanoparticles delivered by BBB opening.
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“Ogawa et al. [83] also used MB-assisted FUS BBB opening to investigate the intravenous delivery of encapsulated mRNA in lipid NPs (mRNA-LNPs) to the brain.”
- Authors
- Ogawa, K., Kato, N., Yoshida, M., Hiu, T., Matsuo, T., Mizukami, S., Omata, D., Suzuki, R., Maruyama, K., Mukai, H., & Kawakami, S.
- Affiliations
- Nagasaki University (JP)
- Teikyo University (JP)
- RIKEN Center for Biosystems Dynamics Research (JP)
- Corresponding author
- Kawakami, Shigeru
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 348
- Pages
- 34-41
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4281642562
- Cited by
- 144
- References
- 45
- Citations by year
- 2026: 40 · 2025: 42 · 2024: 28 · 2023: 26 · 2022: 8
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 304 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Controlled Release (acceptedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Agency for Medical Research and Development (JP21ak0101178)
- Japan Society for the Promotion of Science (21H03818)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- focused ultrasound, microbubbles, blood-brain barrier opening, lipid nanoparticles, mRNA delivery, brain drug delivery, blood-brain barrier permeability, luciferase expression, microglia, endothelial cells, plasmid DNA delivery, intravenous delivery
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Liposomes, Magnetic Resonance Imaging, RNA, Messenger, Drug Delivery Systems, Rats, Sprague-Dawley, Endothelial Cells, Microbubbles, Rats, Nanoparticles
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