Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain

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 foreig...

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Published in:Journal of controlled release 2022-08, Vol.348, p.34-41
Main Authors: Ogawa, Koki, Kato, Naoya, Yoshida, Michiharu, Hiu, Takeshi, Matsuo, Takayuki, Mizukami, Shusaku, Omata, Daiki, Suzuki, Ryo, Maruyama, Kazuo, Mukai, Hidefumi, Kawakami, Shigeru
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Language:English
Subjects:
Blood-brain barrier (BBB)
Focused ultrasound (FUS)
Lipid nanoparticles (LNP)
Messenger RNA (mRNA)
Microbubble
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cited_by cdi_FETCH-LOGICAL-c522t-1bf2049452b807afeca23ba5f7f49fd6242180bf75813076e02ace742465a5963
cites cdi_FETCH-LOGICAL-c522t-1bf2049452b807afeca23ba5f7f49fd6242180bf75813076e02ace742465a5963
container_end_page 41
container_issue
container_start_page 34
container_title Journal of controlled release
container_volume 348
creator Ogawa, Koki
Kato, Naoya
Yoshida, Michiharu
Hiu, Takeshi
Matsuo, Takayuki
Mizukami, Shusaku
Omata, Daiki
Suzuki, Ryo
Maruyama, Kazuo
Mukai, Hidefumi
Kawakami, Shigeru
description 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/cm2, 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. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2022.05.042
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subjects Blood-brain barrier (BBB)
Focused ultrasound (FUS)
Lipid nanoparticles (LNP)
Messenger RNA (mRNA)
Microbubble
title Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain
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