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Molecular design of the membrane-active polyers for spontaneous formation of cell-membrane nanodiscs and their application to nano carriers

Research Project

Project/Area Number 21K19007
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 35:Polymers, organic materials, and related fields
Research InstitutionNara Institute of Science and Technology

Principal Investigator

Yasuhara Kazuma  奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (90545716)

Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsナノディスク / 両親媒性ポリマー / 脂質二分子膜 / ドラッグデリバリー / 自己組織化
Outline of Research at the Start

本研究では、デザインされた高分子によって形成された細胞膜ナノディスクを用いて、特定の細胞小器官へ選択的に分子輸送するナノキャリアを構築することを目的とする。本研究では、研究代表者らがこれまでに開発した膜活性ポリマーを用いた細胞膜ナノディスク技術を核として、新たに細胞へのターゲティング機能を付与したポリマーをデザインすることで、特定の小器官に対して選択的かつ高効率に分子輸送する方法を確立する。

Outline of Final Research Achievements

Molecular transport to cells using nanocarriers plays a crucial role in molecular therapies such as gene therapy and drug delivery systems. In this study, we aimed to construct nanocarriers that selectively transport molecules to specific cellular organelles using lipid nanodiscs formed by designed polymers. The nanodiscs developed in this study were shown to transport molecules to cells more efficiently compared to liposomes, which are widely used as a conventional carrier. Furthermore, it was revealed that encapsulation of anticancer drugs in nanodiscs enhanced their biological activity.

Academic Significance and Societal Importance of the Research Achievements

脂質分子によって構成されるナノキャリアは、カプセル状のリポソームがこれまでその大半を占め、異なる形態を有する脂質分子集合体を用いたキャリア開発は限定的であった。本研究では、リポソームとは異なる形態を有するナノディスクを新たなキャリアとして用いるアプローチによって、リポソームをしのぐ分子輸送特性が実現された。本研究の知見は、年々その重要性を増している分子治療や薬物送達システムの確立において大きく貢献することが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (37 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (18 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 17 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (2 results)

  • [Int'l Joint Research] ミシガン大学(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Lipid cubic phase with an organic?inorganic hybrid structure formed by organoalkoxysilane lipid2024

    • Author(s)
      Kariya Miki、Omoto Kenichiro、Nomura Kaoru、Yonezawa Kento、Kamikubo Hironari、Nishino Toshio、Inoie Tomomi、Rapenne Gw?na?l、Yasuhara Kazuma
    • Journal Title

      Chemical Communications

      Volume: 60 Issue: 16 Pages: 2168-2171

    • DOI

      10.1039/d3cc05167f

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lipid nanodiscs spontaneously formed by an amphiphilic polymethacrylate derivative as an efficient nanocarrier for molecular delivery to intact cells2024

    • Author(s)
      Hao Jinyu、Ishihara Mika、Rapenne Gwenael、Yasuhara Kazuma
    • Journal Title

      RSC Advances

      Volume: 14 Issue: 9 Pages: 6127-6134

    • DOI

      10.1039/d3ra07481a

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Curcumin Modulates the Membrane Raft Integrity via Phase Separation and Induces CD44 Shedding in Tumor Cells2024

    • Author(s)
      Murai, T. et al.
    • Journal Title

      Biochemistry

      Volume: 63 Pages: 441-451

    • DOI

      10.1021/acs.biochem.3c00645

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrothermal Preparation of Faceted Vesicles Made of Span 40 and Tween 40 and Their Characterization2023

    • Author(s)
      Shimanouchi Toshinori、Komori Yui、Toramoto Kazuki、Hayashi Keita、Yasuhara Kazuma、Jung Ho-Sup、Kimura Yukitaka
    • Journal Title

      Applied Sciences

      Volume: 13 Issue: 12 Pages: 6893-6893

    • DOI

      10.3390/app13126893

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HER‐2‐Targeted Boron Neutron Capture Therapy with Carborane‐integrated Immunoliposomes Prepared via an Exchanging Reaction2023

    • Author(s)
      Kawasaki R.、Oshige A.、Yamana K.、Hirano H.、Nishimura K.、Miura Y.、Yorioka R.、Sanada Y.、Bando K.、Tabata A.、Yasuhara K.、Miyazaki Y.、Shinoda W.、Nishimura T.、Azuma H.、Takata T.、Sakurai Y.、Tanaka H.、Suzuki M.、Nagasaki T.、Ikeda A.
    • Journal Title

      Chemistry - A European Journal

      Volume: 29 Issue: 72

    • DOI

      10.1002/chem.202302486

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 自然にまなぶ抗菌・抗ウィルス高分子2023

    • Author(s)
      安原主馬
    • Journal Title

      高分子

      Volume: 72 Pages: 327-330

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Biomimetic antimicrobial polymers – Design, characterization, antimicrobial and novel applications2023

    • Author(s)
      Haruko Takahashi, Iva Sovadinova, Kazuma Yasuhara, Satyavani Vemparala, Gregory A. Caputo, Kenichi Kuroda
    • Journal Title

      WIREs Nanomedicine & Nanobiotechnology

      Volume: 15 Issue: 3

    • DOI

      10.1002/wnan.1866

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nanofluidic Model Membrane for the Single-Molecule Observation of Membrane Proteins2022

    • Author(s)
      Komatsu Ryota、Tanimoto Yasushi、Ando Koji、Yasuhara Kazuma、Iwasaki Yasuhiko、Hayashi Fumio、Morigaki Kenichi
    • Journal Title

      Langmuir

      Volume: 38 Issue: 23 Pages: 7234-7243

    • DOI

      10.1021/acs.langmuir.2c00724

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amyloid-β aggregates induced by β-cholesteryl glucose-embedded liposomes2022

    • Author(s)
      Shimanouchi Toshinori、Sano Yasuhiro、Yasuhara Kazuma、Kimura Yukitaka
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

      Volume: 1870 Issue: 8 Pages: 140816-140816

    • DOI

      10.1016/j.bbapap.2022.140816

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peptide modification on the interior surface of red blood cell ghosts for construction of catalytic reactors2022

    • Author(s)
      Matsumoto Honoka、Okuichi Kentaro、Imamura Hiroshi、Yasuhara Kazuma、Kato Minoru、Koshiyama Tomomi
    • Journal Title

      Chemical Communications

      Volume: 58 Issue: 87 Pages: 12220-12223

    • DOI

      10.1039/d2cc05013g

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Thermally responsive morphological changes of layered coordination polymers induced by disordering/ordering of flexible alkyl chains2022

    • Author(s)
      Omoto Kenichiro、Aoyama Shota、Galica Tomasz、Nishibori Eiji、Katao Shohei、Yasuhara Kazuma、Rapenne Gwenael
    • Journal Title

      Dalton Transactions

      Volume: 51 Issue: 47 Pages: 17967-17972

    • DOI

      10.1039/d2dt03142f

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Creation of supramolecular biomembrane by the bottom-up self-assembly: Where material science meets biophysics2022

    • Author(s)
      Kazuma Yasuhara, Kenichi Morigaki
    • Journal Title

      Biophysics and Physicobiology

      Volume: 19 Issue: 0 Pages: n/a

    • DOI

      10.2142/biophysico.bppb-v19.0043

    • ISSN
      2189-4779
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 生体膜に作用する機能性分子のバイオミメティック・デザイン2022

    • Author(s)
      安原主馬
    • Journal Title

      Acc. Mater. Surf. Res.

      Volume: 7 Pages: 83-91

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Antimicrobial Peptide-Mimetic Methacrylate Random Copolymer Induces Domain Formation in a Model Bacterial Membrane2022

    • Author(s)
      Yasuhara Kazuma、Tsukamoto Manami、Kikuchi Jun-ichi、Kuroda Kenichi
    • Journal Title

      The Journal of Membrane Biology

      Volume: - Issue: 4-5 Pages: 513-521

    • DOI

      10.1007/s00232-022-00220-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanistic Study of Membrane Disruption by Antimicrobial Methacrylate Random Copolymers by the Single Giant Vesicle Method2021

    • Author(s)
      Tsukamoto Manami、Zappala Emanuele、Caputo Gregory A.、Kikuchi Jun-ichi、Najarian Kayvan、Kuroda Kenichi、Yasuhara Kazuma
    • Journal Title

      Langmuir

      Volume: 37 Issue: 33 Pages: 9982-9995

    • DOI

      10.1021/acs.langmuir.1c01047

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Microfluidic and hydrothermal preparation of vesicles using sorbitan monolaurate/polyoxyethylene (20) sorbitan monolaurate (Span 20/Tween 20)2021

    • Author(s)
      Shimanouchi Toshinori、Hayashi Tetsuya、Toramoto Kazuki、Fukuma Saki、Hayashi Keita、Yasuhara Kazuma、Kimura Yukitaka
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 205 Pages: 111836-111836

    • DOI

      10.1016/j.colsurfb.2021.111836

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] アミロイドタンパク質解析のための脂質ナノディスク2021

    • Author(s)
      安原主馬
    • Journal Title

      膜(MEMBRANE)

      Volume: 46(1) Pages: 32-37

    • NAID

      130007977605

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 脂質膜のナノディスク化技術と熱測定への応用2021

    • Author(s)
      安原主馬
    • Journal Title

      熱測定

      Volume: 48(3) Pages: 108-113

    • NAID

      40022660262

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞膜の構造・機能を制御するバイオミメティック高分子の探索2024

    • Author(s)
      安原主馬
    • Organizer
      最先端研究装置とデータの共用が創出するマテリアル研究
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Cellular uptake of spontaneously formed lipid nanodiscs and its size effect2023

    • Author(s)
      Jinyu Hao, Gwenael Rapenne, Kazuma Yasuhara
    • Organizer
      第72回高分子学会年次大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 脂質ナノディスクのドラッグキャリア応用2023

    • Author(s)
      安原主馬, Jinyu Hao, Rapenne Gwenael
    • Organizer
      第33回バイオ・高分子シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] 両親媒性高分子が形成する脂質ナノディスクによる分子デリバリー2023

    • Author(s)
      安原主馬, Jinyu Hao, Rapenne Gwenael
    • Organizer
      第72回高分子討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 両親媒性ポリマーによるジャイアントベシクル曲率の認識2023

    • Author(s)
      安原主馬, 山中諒, 菊池純一, 黒田賢一
    • Organizer
      第74回コロイドおよび界面化学討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Protein-mimetic design of membrane-active polymers2023

    • Author(s)
      Kazuma Yasuhara
    • Organizer
      India-International Science Forum
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 両親媒性高分子による膜活性ペプチドのミメティクス2023

    • Author(s)
      安原主馬
    • Organizer
      分子サイバネティクス・超越分子システム合同シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 合成高分子で膜タンパク質をつくる2022

    • Author(s)
      安原主馬
    • Organizer
      第2回 発動分子科学サロン 「発動分子と分子集合体」
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 両親媒性高分子による脂質ナノディスク形成とナノキャリア応用2022

    • Author(s)
      安原主馬, Jinyu Hao, 光好佑麿, Rapenne Gwenael
    • Organizer
      第71回高分子討論会
    • Related Report
      2022 Research-status Report
  • [Presentation] Lipid nanodisc as a minimal model membrane formed with synthetic polymers2022

    • Author(s)
      安原主馬
    • Organizer
      第60回日本生物物理学会年会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 細胞膜をあやつるポリマーをつくる -膜タンパク質をヒントにした人工分子のデザイン-2021

    • Author(s)
      安原主馬
    • Organizer
      第177回 東海高分子研究会 講演会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 細胞膜の構造・機能制御を目指した両親媒性分子のバイオミメティック・デザイン2021

    • Author(s)
      安原主馬
    • Organizer
      第35回 九州コロイドコロキウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 合成両親媒性分子による脂質膜プラットフォーム2021

    • Author(s)
      安原主馬
    • Organizer
      分子サイバネティクス 第6回領域セミナー
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 両親媒性ポリマーによる脂質二分子膜のナノディスク化と膜物性2021

    • Author(s)
      安原 主馬 岸本 直子, 光好 佑麿, 荒木田 臣, ラッペン ゲナエル
    • Organizer
      第72回コロイドおよび界面化学討論会
    • Related Report
      2021 Research-status Report
  • [Book] Concepts and design of materials nanoarchitectonics2022

    • Author(s)
      K. Yasuhara, K. Omoto, T. Nishino, G. Rapenne (Ed. O. Azzaroni, K. Ariga)
    • Total Pages
      589
    • Publisher
      Royal Society of Chemistry
    • ISBN
      9781788018029
    • Related Report
      2021 Research-status Report
  • [Book] Plasma Membrane Shaping2022

    • Author(s)
      K. Yasuhara (Ed. S. Suetsugu)
    • Publisher
      Elsevier
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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