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2007 Fiscal Year Final Research Report Summary

Development of a high-throughput molecular delivery method using microbubbles and ultrasound and its application to cancer gene therapy

Research Project

Project/Area Number 17300168
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical systems
Research InstitutionTohoku University

Principal Investigator

KODAMA Tetsuya  Tohoku University, Tohoku University, Biomedical Engineering Research Organization, Professor (40271986)

Co-Investigator(Kenkyū-buntansha) ONO Masao  Tohoku University, Graduate School of Medicine, Professor (20302218)
FUJIKAWA Shigeo  Hokkaido University, Graduate School of Engineering, Professor (70111937)
TOMITA Yukio  Hokkaido University of Education, Faculty of Education, Professor (00006199)
Project Period (FY) 2005 – 2007
KeywordsMicrobubble / Gene Therapy / Cancer / Ultrasound / Molecular Delivery
Research Abstract

Non-invasive, tissue-specific molecular delivery is crucial for the efficiency and reduced side effects of a wide range of treatments. A physical method that combines microbubbles (MB) with ultrasound (US) has been regarded as one of the few methods capable of delivering genes into target sites non-invasively. Applied to cancer gene therapy, this method could efficiently target cancer, and may be more efficient than immune gene therapy, as patients are often immunocompromised. However, several essential aspects remain unexplored. First, cavitation bubbles are believed to be a major cause for molecular delivery; however, the relation between wave characteristics and subsequent generation and collapse of cavitation bubbles has not been elucidated, therefore gene transfer has not been optimized. In addition, molecular delivery and subsequent gene expression have not been quantified in vivo. In the present study, these parameters in vitro and in vivo were optimized, and the mechanism of mo … More lecular delivery with theoretical and computer analysis were elucidated. Hypothesizing that free cavitation bubbles were generated from cavitation nuclei created by fragmented MB shells, we estimated the shock wave propagation distance that would induce cell membrane damage from the center of the cavitation bubble. Next, we investigated the structural change of a phospholipid bilayer in water under the action of a shock wave with molecular dynamics simulations. The resulting collapse and rebound of the bilayer followed by the penetration of water molecules into the hydrophobic region of the bilayer induced after the shock wave interaction were demonstrated. Finally, we evaluated the application of this technology to cancer gene therapy using herpes simplex virus thymidine kinase-mediated suicide gene therapy. We observed dramatic reductions of the tumor size by US/MB-mediated transfer. These data demonstrate the potential of US/MB as a new physical gene delivery method for cancer gene therapy. Less

  • Research Products

    (30 results)

All 2008 2007 2006 2005

All Journal Article (22 results) (of which Peer Reviewed: 1 results) Presentation (8 results)

  • [Journal Article] Herpes simplex virus thymidine kinase-mediated suicide gene therapy using nano/microbubbles and ultrasound2008

    • Author(s)
      Aoi A
    • Journal Title

      Ultrasound in Medicine and Biology 34(3)

      Pages: 425-434

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular dynamics simulation of structural changes of lipid bilayers induced by shock waves: effects of incident angles2008

    • Author(s)
      Koshiyama K
    • Journal Title

      Biochimica et Biophysica Acta (BBA) Biomembranes (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Herpes simplex virus thymidine kinase-mediated suicide gene therapy using nano/microbubbles and ultrasound2007

    • Author(s)
      Aoi A
    • Journal Title

      Ultrasound in medicine and Biology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Interaction of shock waves generated by cavitation bubbles with cell Membranes during sonoporation.2007

    • Author(s)
      Kodama T
    • Journal Title

      ICBB2007

      Pages: 7

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular mechanisms of cavitation-induced cell membrane permeabilization.2007

    • Author(s)
      Koshiyama K
    • Journal Title

      ICBB2007

      Pages: 8

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular-scale lipid bilayer response to shock wave: molecular dynamics simulations.2007

    • Author(s)
      Koshiyama K
    • Journal Title

      ABSTRACTS of APCOM'07 in conjunction with EPMESC XI

      Pages: 437

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ソノポレーションによるシスプラチンの導入2007

    • Author(s)
      小玉 哲也
    • Journal Title

      第46回日本生体医工学会大会特別号プログラム・抄録集 45

      Pages: 180

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ソノポレーションによる遺伝子導入効率:気泡特性に対する検討2007

    • Author(s)
      小玉 哲也
    • Journal Title

      日本超音波医学会第80回学術集会プログラム・講演抄録集

      Pages: 295

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ナノバブルと超音波を用いたがん治療法の開発2007

    • Author(s)
      小玉 哲也
    • Journal Title

      日本学術会議第26回混相流シンポジウム講演資料集

      Pages: 10-14

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ナノバブルと超音波を用いたDDS:骨格筋への応用2007

    • Author(s)
      小玉 哲也
    • Journal Title

      日本機械学会2007年度年次大会講演論文集 2

      Pages: 151-152

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 超音波による分子の細胞膜通過機構:分子動力学シュミレーション2007

    • Author(s)
      越山 顕一郎
    • Journal Title

      日本機械学会2007年度年次大会講演論文集 2

      Pages: 153-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] シスプラチンを使った抗腫瘍効果:高周波超音波による定量化2007

    • Author(s)
      冨田 典子
    • Journal Title

      日本機械学会2007年度年次大会講演論文集 2

      Pages: 155-156

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Evaluation of antitumor effects using high frequency ultrasound Biomicroscopy.2007

    • Author(s)
      堀江 佐知子
    • Journal Title

      第66回日本癌学会学術総会

      Pages: 352

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Construction of three-dimentional image of intratumoral vessel using high-fr equency contrast-enhanced micro-ultrasound.2007

    • Author(s)
      冨田 典子
    • Journal Title

      第66回日本癌学会学術総会

      Pages: 353

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Spinal gene transfer using ultrasound and microbubbles2007

    • Author(s)
      Takahashi M
    • Journal Title

      Journal of Controlled Release 117

      Pages: 267-272

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interaction of impulsive pressures of cavitation bubbles with cell membrane during sonoporation2006

    • Author(s)
      Kodama T
    • Journal Title

      AIP Conference Proceedings 829

      Pages: 34-38

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular dynamics simulation of water pore formation in lipid bilayer induced by shock waves2006

    • Author(s)
      Koshiyama K
    • Journal Title

      AIP Conference Proceedings 829

      Pages: 583-587

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transfection effect of microbubbles on cells in superposed ultrasound wzves and behavior of cavitation bubble2006

    • Author(s)
      Kodama T
    • Journal Title

      ultrasound in Medicine and Biology 32(6)

      Pages: 905-914

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structural change of lipid bilayer and water penetration induced by shock wave molecular dynamics simulations2006

    • Author(s)
      Koshiyama K
    • Journal Title

      Biophysical Journal 91(6)

      Pages: 2198-2205

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A non-invasive tissue -specific molecular delivery method of cancer gene therapy2006

    • Author(s)
      Kodama T
    • Journal Title

      Minimally Invasive Therasive Therapy and Allied Technologies 15(4)

      Pages: 226-229

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Delivery of oligodeoxynucleotides into human sphenous veins and the adjunct effect of ultrasound and microbubbles2005

    • Author(s)
      Kodama T
    • Journal Title

      Ultrasound in Medicine and Biology 31(12)

      Pages: 1683-1691

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular delivery into a lipid bilayer with a single shock wave using molecular dynamics simulation2005

    • Author(s)
      Koshiyama K
    • Journal Title

      AIP Conference Proceedings 754

      Pages: 104-106

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Molecular-scale lipid bilayer response to shock wave: molecular dynamics and the Eleventhsimulations2007

    • Author(s)
      Koshiyama K
    • Organizer
      Third Asian-Pacific Congress on Computational Mechanics (APCOM''07) International Conference on the Enhancement and Promotion of Computational Methods in Engineering and Science (EPMESC XI)
    • Place of Presentation
      Kyoto
    • Year and Date
      20071203-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ナノバブルと超音波を用いた高周波超音波三次元画像診断・分子導入システムの開発2007

    • Author(s)
      小玉 哲也
    • Organizer
      ナノバイオテクノロジー連携群成果報告会
    • Place of Presentation
      日本科学未来館
    • Year and Date
      2007-12-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ナノバブルと高周波超音波による腫瘍内血管の三次元画の構築2007

    • Author(s)
      冨田 典子
    • Organizer
      東北大学イノベーションフェア2007 in仙台
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 高周波超音波画像診断によるシスプラチン(CDDP)の抗腫瘍効果の評価2007

    • Author(s)
      堀江 佐知子
    • Organizer
      東北大学イノベーションフェア2007 in仙台
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Antitumor effectiveness of cisplatin with ultrasound and nanobubbles2006

    • Author(s)
      Kodama T
    • Organizer
      152nd Meeting (4th joint meeting of the Acoustical Society of America and the Acoustical Scociety of Japan)
    • Place of Presentation
      Honolulu, Hawaii
    • Year and Date
      20061128-1202
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Delivery of oligodeoxynucleotides into human saphenous veins and the adjunct effect of ultrasound and microbubbles2006

    • Author(s)
      Kodama T
    • Organizer
      American Society of Gene Therapy. The 9th Annual Meeting
    • Place of Presentation
      Baltimore, Maryland
    • Year and Date
      20060531-0604
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Delivery of sodium/iodide symportter therapy using nanobubbles with ultrasound2006

    • Author(s)
      Kodama T
    • Organizer
      The 11th Congress of the World Federation for Ultrasound in Medicine and Bioloy
    • Place of Presentation
      Seoul
    • Year and Date
      20060528-0601
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Nanobubble enhanced drug susceptibility of cancer cells using ultrasound2005

    • Author(s)
      Suzuki M.
    • Organizer
      International Congress Series
    • Year and Date
      20050000
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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