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Development of a nano device to investigate mitochondrial quality control

Research Project

Project/Area Number 17K20076
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering and related fields
Research InstitutionHokkaido University

Principal Investigator

Yamada Yuma  北海道大学, 薬学研究院, 准教授 (60451431)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords薬物送達システム / ミトコンドリア / オートファジー
Outline of Final Research Achievements

Failure of autophagy induction results in the accumulation of abnormal mitochondria and is thought to be a contributing factor to the onset of a variety of progressive neurodegenerative diseases. Relationships between the maintenance of quality of mitochondria and the mechanism responsible for the onset of such diseases have attracted the interest of the scientific community. The aim of this study is to validate that induced autophagy can be activated by delivering autophagy inducing molecules to mitochondria. To achieve efficient mitochondrial delivery, we used a MITO-Porter, a liposome-type nanodevice for mitochondrial delivery via mitochondrial membrane fusion. Autophagy induction was confirmed in HeLa cells by the detection of an autophagy marker, resulting in a remarkable enhancement in autophagy induction caused by the mitochondrial delivery of the autophagy inducing molecules. Our findings constitute additional innovative research findings related to addressing autophagy.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発を進めたミトコンドリアを標的とする人工オートファジー誘導システムは、今までにないアプローチからのミトコンドリア科学を拓き、根本的な治療が難しい進行性神経変性疾患などの疾患解明・治療に大きく貢献することが期待される。さらに、個体レベルでのミトコンドリアを介したオートファジー誘導が実現すれば新たなモデル動物の作出が可能になり、ミトコンドリアが関連する個体レベルの生命現象研究を世界に先駆けて着手することが可能になる。本申請研究で得た知見は、我が国の科学技術発展および新薬開発にも大きく貢献するが期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (28 results)

All 2019 2018 2017 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results) Remarks (4 results)

  • [Journal Article] A Nanocarrier System for Mitochondrial Delivery Targeted to a Pancreatic Beta Cell2019

    • Author(s)
      Yamada Yuma
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 1 Pages: 41-45

    • DOI

      10.1248/yakushi.18-00163-1

    • NAID

      130007541687

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-01-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The use of a microfluidic device to encapsulate a poorly water-soluble drug CoQ10 in lipid nanoparticles and an attempt to regulate intracellular trafficking to reach mitochondria2019

    • Author(s)
      Hibino Mitsue、Yamada Yuma、Fujishita Naoki、Sato Yusuke、Maeki Masatoshi、Tokeshi Manabu、Harashima Hideyoshi
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 印刷中 Issue: 8 Pages: 2668-2676

    • DOI

      10.1016/j.xphs.2019.04.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリア標的型DDSを基盤とした革新的ナノ医薬品の創製2019

    • Author(s)
      山田勇磨
    • Journal Title

      ファルマシア

      Volume: 55 Pages: 330-334

    • NAID

      130007621948

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリアへの分子送達技術2018

    • Author(s)
      山田勇磨、原島秀吉
    • Journal Title

      BIO Clinica

      Volume: 33 Pages: 637-640

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Mitochondrial Delivery of Doxorubicin Using MITO-Porter Kills Drug-Resistant Renal Cancer Cells via Mitochondrial Toxicity2017

    • Author(s)
      Yamada Yuma、Munechika Reina、Kawamura Eriko、Sakurai Yu、Sato Yusuke、Harashima Hideyoshi
    • Journal Title

      J Pharm Sci

      Volume: 106 Issue: 9 Pages: 2428-2437

    • DOI

      10.1016/j.xphs.2017.04.058

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Packaging of the Coenzyme Q<sub>10</sub> into a Liposome for Mitochondrial Delivery and the Intracellular Observation in Patient Derived Mitochondrial Disease Cells2017

    • Author(s)
      Yamada Yuma、Burger Laila、Kawamura Eriko、Harashima Hideyoshi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 12 Pages: 2183-2190

    • DOI

      10.1248/bpb.b17-00609

    • NAID

      130006235437

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Optical control of mitochondrial reductive reactions in living cells using an electron donor?acceptor linked molecule2017

    • Author(s)
      Takano Yuta、Munechika Reina、Biju Vasudevanpillai、Harashima Hideyoshi、Imahori Hiroshi、Yamada Yuma
    • Journal Title

      Nanoscale

      Volume: 9 Issue: 47 Pages: 18690-18698

    • DOI

      10.1039/c7nr06310e

    • NAID

      120006545088

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] オートファジー誘導能を有するミトコンドリアDDSの構築およびオートファジー誘導機構の検証2019

    • Author(s)
      山田勇磨、大工原伸之輔、西田慶、田村篤志、由井伸彦、原島秀吉
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mitochondrial Nano DDS Toward Innovative Medicine and Therapy.2018

    • Author(s)
      Yamada Y
    • Organizer
      HIGO Program Cutting edge Seminar.
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリアDDSの使い方2018

    • Author(s)
      山田勇磨
    • Organizer
      第9回 フリーラジカルスクール
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリア機能を制御するナノカプセルの構築および疾患治療に向けた試み2018

    • Author(s)
      山田 勇磨、原島秀吉
    • Organizer
      第91回 日本生化学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Mitochondrial DDS opens emerging therapies and novel strategy of new drug development for mitochondrial disorders.2018

    • Author(s)
      Yamada Y, Harashima H
    • Organizer
      KSAP annual convention 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ミトコンドリア標的型DDSを基盤としたナノ医療の創出を目指して2018

    • Author(s)
      山田 勇磨、原島秀吉
    • Organizer
      第18回 日本ミトコンドリア学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The MITO-Porter integrates a mitochondrial drug delivery system with a variety of other current scientific concepts with the goal of developing new innovative technologies and medicines.2018

    • Author(s)
      Yamada Y, Harashima H
    • Organizer
      The 19th RIES-HOKUDAI International Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エネルギー産生能を亢進するビタミンB1封入ミトコンドリア標的型ナノキャリアの構築2018

    • Author(s)
      石丸拓也、山田勇磨、原島秀吉
    • Organizer
      日本薬学会北海道支部第145回例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TCAサイクルを活性化するビタミンB1封入ミトコンドリア標的型DDSの構築2018

    • Author(s)
      石丸拓也、山田勇磨、原島秀吉
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミトコンドリア機能を制御するナノカプセルの開発2018

    • Author(s)
      山田勇磨
    • Organizer
      第6回ミトコンドリア機能研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 膵島ミトコンドリアを標的とした分子送達技術の開発および糖尿病治療への展開2018

    • Author(s)
      山田勇磨
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ミトコンドリアを診る・操る・治すDrug Delivery System2017

    • Author(s)
      山田勇磨
    • Organizer
      第2回先端ケミカルバイオロジー研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] ミトコンドリアDDSの開発と医療分野への展開2017

    • Author(s)
      山田勇磨
    • Organizer
      第11回 次世代を担う若手医療薬科学シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 癌細胞ミトコンドリアを標的とした光殺細胞効果の検証2017

    • Author(s)
      山田 勇磨、高野勇太、宗近玲那、福田豊、今堀博、原島秀吉
    • Organizer
      第70回日本酸化ストレス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Validation of autophagy induction via the mitochondrial delivery of Polyrotaxane by a MITO-Porter2017

    • Author(s)
      Daikuhara S, Yamada Y, Tamura A, Nishida K, Yui N, Harashima H.
    • Organizer
      The 2nd International Symposium on Biomedical Engineering
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] オートファジー誘導能を有する超分子構造ポリマー搭載 MITO-Porter の構築および機能評価2017

    • Author(s)
      大工原伸之輔、山田勇磨、原島秀吉
    • Organizer
      日本薬学会北海道支部第144回例会
    • Related Report
      2017 Research-status Report
  • [Presentation] オートファジー誘導能を有する超分子構造ポリマー搭載ミトコンドリアDDSの構築2017

    • Author(s)
      大工原伸之輔、山田 勇磨、田村篤志、西田慶、由井伸彦、原島秀吉
    • Organizer
      第33回日本DDS学会
    • Related Report
      2017 Research-status Report
  • [Remarks] 北海道大学 大学院薬学研究院 薬剤分子設計学研究室HP

    • URL

      https://www.pharm.hokudai.ac.jp/yakusetu/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 北海道大学 大学院薬学研究院 HP

    • URL

      https://www.pharm.hokudai.ac.jp/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 7SEAS PROJECT HP

    • URL

      https://7sp.life/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] ルカ・サイエンス

    • URL

      https://luca-science.com/

    • Related Report
      2018 Annual Research Report

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Published: 2017-07-21   Modified: 2020-03-30  

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