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Development of Multi-layered nano-device for mitochondrial drug delivery and an innovative approach for mitochondrial disease' therapy

Research Project

Project/Area Number 21700483
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biomedical engineering/Biological material science
Research InstitutionHokkaido University

Principal Investigator

YAMADA Yuma  Hokkaido University, 大学院・薬学研究院, 助教 (60451431)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords薬学 / ミトコンドリア / バイオテクノロジー / 癌 / 細胞・組織 / ナノテクノロジー / 遺伝子送達 / タンパク質送達 / イメージング / 細胞内動態制御
Research Abstract

Mitochondrial dysfunction is associated with a variety of human diseases. Effective medical therapies for mitochondrial diseases will ultimately require an optimal drug delivery system, which will likely be achieved through innovations in the nanotechnology of intracellular trafficking. To achieve efficient mitochondrial drug delivery, two independent processes, i.e., "cytoplasmic delivery through the cell membrane" and "mitochondrial delivery through the mitochondrial membrane" are required. Here, we report the development of a Dual Function MITO-Porter (DF-MITO-Porter), a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery. We show that the DF-MITO-Porter effectively delivers exogenous macro-biomolecules into the mitochondrial matrix, and provide a demonstration of its potential use in therapies aimed at mitochondrial DNA.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (35 results)

All 2011 2010 2009 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (22 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake.2011

    • Author(s)
      R.Furukawa, Y.Yamada, M.Takenaga, R.Igarashi, H.Harashima.
    • Journal Title

      Biochem.Biophys.Res.Commun. 404

      Pages: 796-801

    • NAID

      120002834731

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake.2011

    • Author(s)
      古川亮、山田勇磨(First author)、武永美津子、五十嵐理慧、原島秀吉
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 404 Pages: 796-801

    • NAID

      120002834731

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial matrix delivery using a MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes.2010

    • Author(s)
      Y.Yasuzaki, Y.Yamada, H.Harashima.
    • Journal Title

      Biochem.Biophys.Res.Commun. 397

      Pages: 181-186

    • NAID

      120002834836

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intranuclear DNA Release is a Determinant of Transfection Activity for a Non-viral vector : Biocleavable Polyrotaxane as a Supramolecularly Dissociative Condenser for Efficient Intranuclear DNA Release.2010

    • Author(s)
      Y.Yamada, T.Nomura, H.Harashima, A.Yamashita, R.Katoono, N.Yui.
    • Journal Title

      Biol.Pharm.Bull. 33

      Pages: 1218-1222

    • NAID

      130000300290

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial matrix delivery using a MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes.2010

    • Author(s)
      安崎友香理、山田勇磨(First author)、原島秀吉
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 397 Pages: 181-186

    • NAID

      120002834836

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intranuclear DNA Release is a Determinant of Transfection Activity for a Non-viral vector : Biocleavable Polyrotaxane as a Supramolecularly Dissociative Condenser for Efficient Intranuclear DNA Release.2010

    • Author(s)
      山田勇磨、野村卓、原島秀吉、山下敦、上遠野亮、由井伸彦
    • Journal Title

      Biological & Pharmaceutical Bulletin

      Volume: 33 Pages: 1218-1222

    • NAID

      130000300290

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transgene expression efficiency from plasmid DNA delivered as a complex with histone H3.2010

    • Author(s)
      紙谷浩之、後藤仁美、神田元紀、山田勇磨、原島秀吉
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 392 Pages: 249-253

    • NAID

      120002208933

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual Function MITO-Porter, a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery.

    • Author(s)
      Y.Yamada, R.Furukawa, Y.Yasuzaki, H.Harashima.
    • Journal Title

      Mol.Ther. (in press)

    • NAID

      120003898268

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] ミトコンドリアとDDS~日本発・世界初の研究・技術・創薬を目指して~若手研究者公開特別シンポジウムミトコンドリアとDDS12011

    • Author(s)
      山田勇磨
    • Organizer
      (オーガナイザー:山田勇磨)
    • Place of Presentation
      札幌
    • Year and Date
      2011-01-21
    • Related Report
      2010 Final Research Report
  • [Presentation] ミトコンドリアとDDS~日本発・世界初の研究・技術・創薬を目指して~2011

    • Author(s)
      山田勇磨
    • Organizer
      若手研究者公開特別シンポジウム ミトコンドリアとDDS 1
    • Place of Presentation
      札幌(北海道大学)(招待講演)
    • Year and Date
      2011-01-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] ミトコンドリア標的型DDS、MITO-Porterを用いたオリゴ核酸送達の試み2011

    • Author(s)
      河村恵理子、山田勇磨、原島秀吉
    • Organizer
      日本薬学会 第131年会
    • Place of Presentation
      静岡(ツインメッセ静岡)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Dual Function MITO-Porter, an innovative nano-carrier system for mitochondrial drug delivery2010

    • Author(s)
      Y.Yamada, R.Furukawa, Y.Yasuzaki, H.Harashima.
    • Organizer
      FIP Pharmaceutical Sciences World Congress (PSWC) 2010.
    • Place of Presentation
      New Orleans, USA.
    • Related Report
      2010 Final Research Report
  • [Presentation] Membrane fusions open a new avenue for mitochondrial delivery : Dual Function MITO-Porter, a nano-carrier system with cell and mitochondrial membranes-fusogenic activity2010

    • Author(s)
      Y.Yamada, R.Furukawa, Y.Yasuzaki, H.Harashima.
    • Organizer
      International liposome research days & lipids liposomes & membrane biophysic.
    • Place of Presentation
      Vancouver, Canada.
    • Related Report
      2010 Final Research Report
  • [Presentation] “ボンクレキン酸(抗アポトーシス作動薬)搭載ミトコンドリア標的型DDS(MITO-Porter)の開発2010

    • Author(s)
      山田勇磨、河村恵理子、安崎友香理、新藤充、原島秀吉
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Membrane fusions open a new avenue for mitochondrial delivery : Dual Function MITO-Porter, a nano-carrier system with cell and mitochondrial membranes-fusogenic activity2010

    • Author(s)
      山田勇磨、古川亮、安崎友香理、原島秀吉
    • Organizer
      International liposome research days & lipids liposomes & membrane biophysic
    • Place of Presentation
      Vancouver, Canada (University of British Columbia Campus)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Octaarginine-modified liposome enhances anti-oxidant effect of PC-SOD through the improvement of intracellular trafficking2010

    • Author(s)
      古川亮、山田勇磨、武永美津子、五十嵐理慧、原島秀吉
    • Organizer
      International liposome research days & lipids liposomes & membrane biophysic
    • Place of Presentation
      Vancouver, Canada (University of British Columbia Campus)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Lighting a candle in mitochondria : Visualization of mitochondrial DNA using MITO-Porter, which is nano-device for mitochondrial delivery2010

    • Author(s)
      安崎友香理、山田勇磨、原島秀吉
    • Organizer
      International liposome research days & lipids liposomes & membrane biophysic
    • Place of Presentation
      Vancouver, Canada (University of British Columbia Campus)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Dual Function MITO-Porter, an innovative nano-carrier system for mitochondrial drug delivery2010

    • Author(s)
      山田勇磨、古川亮、安崎友香理、原島秀吉
    • Organizer
      FIP Pharmaceutical Sciences World Congress (PSWC) 2010
    • Place of Presentation
      New Orleans, USA (Morial Convention Center)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 効率的な細胞内導入を目的としたレシチン化SOD(PC-SOD)搭載R8リポソームの構築およびその機能評価2010

    • Author(s)
      古川亮、山田勇磨、武永美津子、五十嵐理慧、原島秀吉
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      徳島(あわぎんホール)
    • Related Report
      2010 Annual Research Report
  • [Presentation] DDS技術を基盤とした生細胞ミトコンドリアDNAの可視化2010

    • Author(s)
      安崎友香理、山田勇磨、原島秀吉
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      徳島(あわぎんホール)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 生細胞ミトコンドリアDNAセンシング技術の開発2010

    • Author(s)
      安崎友香理,山田勇磨、原島秀吉
    • Organizer
      遺伝子・デリバリー研究会 第10回シンポジウム
    • Place of Presentation
      札幌(北海道大学)
    • Related Report
      2010 Annual Research Report
  • [Presentation] ボンクレキン酸(抗アポトーシス作動薬)搭載ミトコンドリア標的型DDS(MITO-Porter)の開発2010

    • Author(s)
      山田勇磨、河村恵理子、安崎友香理、新藤充、原島秀吉
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪(大阪国際交流センター)
    • Related Report
      2010 Annual Research Report
  • [Presentation] ミトコンドリア標的型ナノデバイス"多重型MITO-Porter"の創製2009

    • Author(s)
      山田勇磨, 古川亮, 安崎友香理, 原島秀吉
    • Organizer
      第9回日本ミトコンドリア学会年会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] MITO-PORTER : A LIPOSOME-BASED NANO-DEVICE FOR MITOCHONDRIAL MACROMOLECULE DELIVERY VIA MEMBRANE FUSION ?INNOVATIVE STRATEGY AIMED FOR MITOCHONDRIAL GENE THERAPY-2009

    • Author(s)
      Y.Yamada, Y.Yasuzaki, R.Furukawa, H.Harashima.
    • Organizer
      Joint Symposium of the 5th Annual Meeting of the Oligonucleotide Therapeutics Society and the 19th Antisense Symposium.
    • Place of Presentation
      Fukuoka, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] "ミトコンドリア標的型ナノデバイス"多重型MITO-Porter"の製剤化に関する検討2009

    • Author(s)
      山田勇磨, 古川亮, 安崎友香理, 原島秀吉
    • Organizer
      第25回日本DDS学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] "ミトコンドリア標的型ナノデバイス"多重型MITO-Porter"の有用性の検証2009

    • Author(s)
      山田勇磨, 古川亮, 安崎友香理, 原島秀吉
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Related Report
      2010 Final Research Report
  • [Presentation] A LIPOSOME-BASED NANO-DEVICE FOR MITOCHONDRIAL MACROMOLECULE DELIVERY VIA MEMBRANE FUSION-INNOVATIVE STRATEGY AIMED FOR MITOCHONDRIAL GENE THERAPYMITO-PORTER-2009

    • Author(s)
      山田勇磨
    • Organizer
      Joint Symposium of the 5th Annual Meeting of the Oligonucleotide Therapeutics Society and the 19th Antisense Symposium
    • Place of Presentation
      Fukuoka, Japan(Centennial Hall, Kyushu University Hospital Campus)
    • Related Report
      2009 Annual Research Report
  • [Presentation] ミトコンドリア標的型ナノデバイス"多重型MITO-Porter"の有用性の検証2009

    • Author(s)
      山田勇磨
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡(静岡コンベンションアーツセンター)
    • Related Report
      2009 Annual Research Report
  • [Presentation] ミトコンドリア標的型ナノデバイス"多重型MITO-Porter"の製剤化に関する検討2009

    • Author(s)
      山田勇磨
    • Organizer
      第25回日本DDS学会
    • Place of Presentation
      東京(東京ドームホテル)
    • Related Report
      2009 Annual Research Report
  • [Presentation] ミトコンドリア標的型ナノデバイス"多重型MITO-Porter"の創製2009

    • Author(s)
      山田勇磨
    • Organizer
      第9回日本ミトコンドリア学会年会
    • Place of Presentation
      東京(東京大学医学部鉄門記念講堂)
    • Related Report
      2009 Annual Research Report
  • [Book] Organelle-Specific Pharmaceutical Nanotechnology2011

    • Author(s)
      Volkmar Weissig
    • Publisher
      Wiley A John Wiley & Sons, Inc.
    • Related Report
      2010 Annual Research Report
  • [Book] Chapter 25 Uptake Pathways Dependent Intracellular Trafficking of DNA Carrying Nanodelivery System(Organelle-Specific Pharmaceutical Nanotechnology, Editors : Volkmar Weissig and Gerard G.M. D'Souza Wiley A John Wiley & Sons, Inc., Publication)2010

    • Author(s)
      I.A.Khalil, Y.Yamada, H.Akita, H.Harashima
    • Related Report
      2010 Final Research Report
  • [Book] 多機能性エンベロープ型ナノ構造体(MEND)を基盤とした新規タンパク質DDSの構築と臨床開発研究への応用(ペプチド・タンパク性医薬品の新規DDS製剤の開発と応用-遺伝子医学MOOK別冊)(編集:山本昌)

    • Author(s)
      山田勇磨, 中村孝司、原島秀吉
    • Publisher
      メディカル ドゥ(in press)
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://www.pharm.hokudai.ac.jp/yakusetu/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.pharm.hokudai.ac.jp/yakusetu/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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