Elucidation of mechanisms and expansion of application range of sonoporation by in situ observation of bubble-cell interaction
| Project/Area Number |
17H00864
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical systems
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| Research Institution | Hokkaido University |
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Principal Investigator |
Kudo Nobuki 北海道大学, 情報科学研究院, 准教授 (30271638)
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| Co-Investigator(Kenkyū-buntansha) |
松崎 典弥 大阪大学, 工学研究科, 教授 (00419467)
鈴木 亮 帝京大学, 薬学部, 教授 (90384784)
佐々木 東 北海道大学, 獣医学研究院, 助教 (00754532)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥33,150,000 (Direct Cost: ¥25,500,000、Indirect Cost: ¥7,650,000)
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| Keywords | 超音波治療 / ソノポレーション / 血液脳関門開放 / 薬物送達 / マイクロバブル / 高速度観察 / 血管内皮細胞 / ３次元細胞培養 / 微小気泡 / 高速度顕微観察 / 3次元細胞培養 / 毛細血管 / 樹状細胞 / 側方観察 / ファインバブル / 細胞培養 |
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| Outline of Final Research Achievements |
Sonoporation and blood-brain (tumor) barrier (BBB/BTB) opening techniques achieve local drug delivery by ultrasound irradiation with microbubbles. The former delivers drugs into cells by increasing the cell membranes permeability, and the latter facilitates drug transfer from blood to perivascular tissues by loosening vascular endothelial cell junctions. In this study, we created three models that simulate the in vivo situation in which three types of cells exist: superficial cells on the soft tissue, vascular endothelial cells that manage drug transfer from the blood, and dendritic cells that are responsible for immunity. The cell-bubble interaction in the model was observed in situ using high-speed confocal microscope to elucidate the mechanisms of sonoporation and blood barrier opening and their dependence on ultrasound irradiation conditions.
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| Academic Significance and Societal Importance of the Research Achievements |
ソノポレーションや血液脳（腫瘍）関門の開放の実現に向け，実験動物を用いる検討は盛んに行われているが，ごく少数を除き臨床応用には至っていない．その原因は，超音波周波数で起きる細胞レベルの変化の観察が工学的に困難であり，現象の基礎的理解が不十分なまま応用研究が先行したことにある．本研究では，現象の解明鳥飼いを目指して世界最高性能を有する観察システムを開発するとともに，生体内を模擬するモデルを開発し，生体内で実際に起きている現象の機序を解明した．本研究成果を端緒に現象の理解が進めばソノポレーション・薬物送達・免疫治療の促進など，超音波を用いた低侵襲治療法の実用性が大幅な進歩が見込まれる．
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Report
(4 results)
Research Products
(100 results)
