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Direct cytoplasmic delivery of protein drugs by electric field-driven cell membrane-permeable peptide nanoneedles

Research Project

Project/Area Number 19K12800
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKyoto Institute of Technology

Principal Investigator

Waku Tomonori  京都工芸繊維大学, 分子化学系, 准教授 (30548699)

Co-Investigator(Kenkyū-buntansha) 小堀 哲生  京都工芸繊維大学, 分子化学系, 教授 (00397605)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsドラッグデリバリーシステム / 自己組織化 / ペプチド / ナノ材料 / ナノファイバー / 超分子重合 / 超分子ポリマー / 超分子 / ナノテクノロジー
Outline of Research at the Start

がんや免疫疾患などの難治疾患の治療に有効な蛋白質医薬が注目を集めている。しかしながら、蛋白質医薬を細胞の中(細胞質)に到達させることが困難であるため、これがネックとなり蛋白質医薬の普及には至っていない。研究代表者は、ニードル形状のペプチドナノ集合体を、電場駆動でまさに針のように細胞膜透過させることができれば、これをキャリアに用いることでタンパク質医薬を細胞質に直接送達することができるのではないかと考えた。本研究では、電場駆動型の細胞膜透過性ペプチドナノニードルを、ペプチドの自己集合を精密に制御することで作製するとともに、コンセプトの実証をin vitroとin vivoで行う。

Outline of Final Research Achievements

Aiming at the development of a carrier for cytoplasmic delivery of protein drugs, we have developed a technique for preparing peptide nanofibers with a multi-block structure as an element technology necessary for the preparation. Even with combinations of seeds and monomers with different compositions, if the fibril-forming sequences were common, fibers were elongated from the seeds, and nanofibers with a multi-block structure consisting of heterogeneous segments were formed. It was also found that the length of each segment can be freely controlled.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発したマルチブロック構造を有するペプチドナノファイバーの作製技術は、従来の高分子ミセルなどの球状キャリアとは異なる機能を有する新たなドラッグデリバリーキャリアの開発に役立つと期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2022 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] βシートペプチドを基盤とするナノファイバーメディシンの開発2022

    • Author(s)
      和久友則
    • Journal Title

      バイオマテリアル

      Volume: 40 Pages: 224-229

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Development of a brain-permeable peptide nanofiber that prevents aggregation of Alzheimer pathogenic proteins2020

    • Author(s)
      Tanaka N, Okuda M, Nishigaki T, Tsuchiya N, Kobayashi Y, Uemura T, Kumo S, Sugimoto H, Miyata S, Waku T.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 7 Pages: e0235979-e0235979

    • DOI

      10.1371/journal.pone.0235979

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation on the interactions between self-assembled β-sheet peptide nanofibers and model cell membranes2020

    • Author(s)
      Waku T., Kasai A., Kobori A., Tanaka N.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 24 Pages: 9518-9518

    • DOI

      10.3390/ijms21249518

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ice-phobic glass-substrate surfaces coated with polypeptides inspired by antifreeze protein2020

    • Author(s)
      K. Koshio, T. Waku and Y. Hagiwara
    • Journal Title

      International Journal of Refrigeration

      Volume: 114 Pages: 201-209

    • DOI

      10.1016/j.ijrefrig.2020.01.025

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Amyloid β Fibrillation by Nanoparticles Composed of Ovalbumin-derived Amphiphilic Peptides2020

    • Author(s)
      Waku Tomonori、Kobayashi Yukako、Wada Mei、Hamawaki Taiga、Handa Akihiro、Okuda Michiaki、Sugimoto Hachiro、Kobori Akio、Tanaka Naoki
    • Journal Title

      Chemistry Letters

      Volume: 49 Issue: 4 Pages: 383-385

    • DOI

      10.1246/cl.200048

    • NAID

      130007828855

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of nanomedicine based on β-sheet peptide nanofibers2022

    • Author(s)
      Tomonori Waku
    • Organizer
      International Congress on Pure & Applied Chemistry (ICPAC) Kota Kinabalu 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗原を担持した細胞内環境応答性ペプチドナノファイバーの 設計と機能評価2019

    • Author(s)
      横山知沙・和久友則・小堀哲生・田中直毅
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ペプチドナノファイバーの線維長精密制御と抗原デリバリー キャリアへの応用2019

    • Author(s)
      西山魁人・和久友則・小堀哲生・田中直毅
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 卵殻膜ペプチドを修飾した電界紡糸 PVA ナノファイバーの 作製と細胞培養基板への応用2019

    • Author(s)
      吉川貴士・和久友則・小堀哲生・田中直毅
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗原を担持した細胞内環境応答性ペプチドナノファイバー の作製と機能評価2019

    • Author(s)
      横山知沙・和久友則・小堀哲生・田中直毅
    • Organizer
      第68回高分子討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] 線維長の制御されたペプチドナノファイバーの精密作製と 抗原デリバリーキャリアへの応用2019

    • Author(s)
      西山魁人・和久友則・小堀哲生・田中直毅
    • Organizer
      第68回高分子討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] 線維長の制御されたペプチドナノファイバーの精密作製と抗原デリバリーキャリアへの応用2019

    • Author(s)
      和久友則・小枝清花・小堀哲生・田中直毅
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Design of Intracellular Environment-responsive Peptide Nanofibers for Antigen Delivery2019

    • Author(s)
      Tomonori Waku・Akio Kobori・Naoki Tanaka
    • Organizer
      5th International Symposium on Advances in Sustainable Polymers
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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