| Project/Area Number |
17H07128
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Research Collaborator |
SAITO Kiyosumi
ONO Kota
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | リポソーム / 超音波 / miRNA / 脳標的ペプチド / ナノバブル / 核酸搭載 / ペプチド / 脳 |
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| Outline of Final Research Achievements |
In this study, we attempted to prepare nucleic acid-loaded and brain-targeting nanobubbles (NBs) modified with Angiopep-2 (Ang2) peptide. Ang2 is expected to be a useful ligand for the efficient delivery of nanocarriers to the brain. We showed that nucleic acid-loaded cationic NBs modified with Ang2 interacted with brain-derived endothelial cells. To enhance the stability, targeting ability, and transfection effect in vivo, we attempted nucleic acid loading to anionic NBs which is already showed the stability in vivo. It was cleared that zeta potential of anionic NBs was inverted to positive by cationic polysaccharide coating and polysaccharide-coated NBs could load nucleic acids onto the surface. Furthermore, polysaccharide-coated NBs could deliver miRNA into cells with ultrasonic irradiation and polysaccharide coating had no effect on the ultrasound contrast ability. Our polysaccharide-coated NBs could be an effective diagnostic and therapeutic tools.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、アニオン性脂質含有ナノバブルへの核酸搭載法を新たに開発した。これは生体内で安定なアニオン性ナノバブルへ負電荷を有する核酸の搭載を可能とするものである。ナノバブルの生体内安定性が増大することは、in vivoにおける超音波造影効果の持続はもちろん、導入の駆動力となるナノバブルが安定に存在することで、導入効果の向上が可能となる。また本法は、核酸に限らず、遺伝子や負電荷を有する治療用分子のデリバリーツールとしても適用可能となることから、その対象疾患も広く汎用性の高い製剤開発に繋がることが期待される。
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