2019 Fiscal Year Final Research Report
Design of membrane permeated nanocarriers with avoiding drug-resistant transporters
| Project/Area Number |
17H02096
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中山 勝文 立命館大学, 薬学部, 教授 (20453582)
最上 譲二 東北大学, 工学研究科, 助教 (70713022)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | スルホベタインポリマー / 薬物送達 / 細胞膜透過 |
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| Outline of Final Research Achievements |
Sulfobetaine polymers were succeeded to localize in the mitochondria with maintaining the mitochondrial enzyme activity by conjugation with Rhodamine B, a fluorescent dye that localizes to mitochondria. Next, the anticancer drugs were conjugated the sulfobetaine polymers. The drug conjugated sulfobetaine polymers diffuses and localizes not only in monolayer cultured cells but also in cells located inside the 3D cell aggregates. The anti-cancer drug conjugated polymers exhibited the drug efficacy to the 3D cell aggregates. On the other hand, we succeeded to synthesize a novel temperature-responsive sulfobetaine polymers in which the polymer itself directivity localize to the mitochondria. Anticancer drugs were succeeded to deliver the mitochondria by conjugation with sulfobetaine polymer.
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| Free Research Field |
ポリマーバイオマテリアル
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| Academic Significance and Societal Importance of the Research Achievements |
細胞膜障害性を最低限にとどめ、膜透過を示すポリマーは極めて少数しか知られていない。その1つであるスルホベタインポリマーの構造と細胞機能について詳細に解析することは、ポリマーの高機能化・多機能化を導き多くの薬物のキャリアとして、また高分子医薬としての開発も期待される。さらに、本成果では三次元培養細胞に対する良好な透過・拡散・局在化を可能としたが、このことは三次元細胞凝集塊を用いた信頼性の高い創薬評価を一般化する技術となりうる。つまり社会的要請の強い動物実験の減数のみならず、開発期間の短縮・費用の抑制に伴う薬価の低減にも寄与するため、その社会的意義は大きい。
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