| Project/Area Number |
18H03531
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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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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
樋口 ゆり子 京都大学, 薬学研究科, 准教授 (40402797)
宗 可奈子 京都大学, 薬学研究科, 助教 (50816684)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | ドラッグデリバリーシステム / 細胞内標的指向化 / 糖鎖 / 小胞体 / 逆行性輸送 / ドラッグデリバリー |
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| Outline of Final Research Achievements |
Med-size or macromolecular drugs are expected to have high potency and high selectivity for therapeutic targets, but their cell membrane permeability is severely limited. In this study, we developed drug delivery systems that utilizes selective transport mechanisms of intracellular vesicles to transport drugs from outside the cell to targeted intracellular organelles. By modifying nanoparticles composed of lipids or block co-polymers and proteins containing low molecular weight antibodies with carbohydrate ligands such as sialyl Lewis X and hyaluronic acid, the transport to the endoplasmic reticulum and cytoplasm was promoted, thereby enhancing the therapeutic effect of bioactive substances. Because these systems can deliver macromolecules such as low-molecular-weight antibodies effectively, they would be able to expand the range of therapeutic targets and contribute to the development of new drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞表面の形質膜で認識されて内在化された高分子や粒子はリソソーム分解経路に移行するが、本研究で開発した糖鎖リガンド修飾薬物デリバリーシステムは抗体医薬品等を安定に細胞内小器官に輸送する。抗体医薬品は細胞外あるいは細胞表面を標的とするものしか開発できなかった。一方、細胞内情報伝達の多くはタンパク質間相互作用により起こるが、これは低分子薬物では制御できないという問題もある。本システムにより低分子抗体等高分子物質を必要な部位に送達できれば様々な適用が可能となり、新しい医薬品の創製に貢献できると期待される。
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