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Development of innovative cancer treatment technology by enhancing intratumoral penetration and cellular uptake of nanoparticles by weak electric current

Research Project

Project/Area Number 17H03976
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

KOGURE Kentaro  徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (70262540)

Co-Investigator(Kenkyū-buntansha) 南川 典昭  徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (40209820)
田中 保  徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 教授 (90258301)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Keywordsドラッグデリバリー / 微弱電流 / ナノ粒子 / がん治療 / 微弱電流処理
Outline of Final Research Achievements

The purpose of this study was to establish an efficient cancer treatment method by enhancing the EPR effect and inducing intracellular uptake of nanoparticles by iontophoresis (IP). We succeeded in increasing the tumor accumulation of nanoparticles administered intravenously to tumor-bearing mice by about 2 times by IP. We also found that IP increased FITC-labeled dextran leakage in embryonic chicken eggs by about 2-fold. We also found that tumor tissue IP reduced the expression level of connexin Cx43 and promoted phosphorylation, activated GTPase through Hsp90 protein activation, and induced unique endocytosis. In addition, the combination of IP and anti-cancer nanoparticles tended to suppress tumor growth more than administration of nanoparticles alone.

Academic Significance and Societal Importance of the Research Achievements

微弱電流を用いる薬物送達技術イオントフォレシスによって、腫瘍組織の生理機能を変化させることで、ナノ粒子等の薬物送達効率を向上させることに成功したことは、世界で初めての成果であり、がん治療薬物領域の発展に大きく貢献するものである。また、近年ヒトのがんでは、EPR効果が見られないとも言われているが、イオントフォレシスを組合わせることでEPR効果を誘起することが可能になり、がん治療効果の増強に繋がることから、国民の健康福祉に貢献することが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] Characteristics of unique endocytosis induced by weak current for cytoplasmic drug delivery2020

    • Author(s)
      Torao Tasuku、Mimura Miyuki、Oshima Yasufumi、Fujikawa Koki、Hasan Mahadi、Shimokawa Tatsuharu、Yamazaki Naoshi、Ando Hidenori、Ishida Tatsuhiro、Fukuta Tatsuya、Tanaka Tamotsu、Kogure Kentaro
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 576 Pages: 119010-119010

    • DOI

      10.1016/j.ijpharm.2019.119010

    • NAID

      120006951318

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low Electric Treatment activates Rho GTPase via Heat Shock Protein 90 and Protein Kinase C for Intracellular Delivery of siRNA.2019

    • Author(s)
      Hasan M, Hama S, Kogure K.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 4114-4114

    • DOI

      10.1038/s41598-019-40904-z

    • NAID

      120006872363

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 発育鶏卵を用いた微弱電流処理による血管透過性亢進の検討2020

    • Author(s)
      中谷奈津, 福田達也, 小暮健太朗.
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Weak Current-mediated delivery of liposomes.2019

    • Author(s)
      Kogure K.
    • Organizer
      Liposome Research Days 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 微弱電流を用いた核酸医薬送達2019

    • Author(s)
      小暮健太朗
    • Organizer
      日本核酸医薬学会DDS部会主催合同サテライトシンポジウム2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Acceleration of the enhanced permeability and retention effect for delivery of nanoparticles by treatment with weak current.2019

    • Author(s)
      Mimura M, Khatun A, Natatani N, Fukuta T, Kogure K.
    • Organizer
      Liposome Research Days 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微弱電流による特殊なエンドサイトーシスを利用した高分子送達の機構解析2018

    • Author(s)
      福田達也, 虎尾 祐, 三村美夕紀, 大島康史, 中谷奈津, 田中 保, 小暮健太朗
    • Organizer
      第18回遺伝子・デリバリー研究会第18回夏期セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanistic study of faint electric treatment mediated cytoplasmic delivery of siRNA2018

    • Author(s)
      Hasan M, Hama S, Kogure K
    • Organizer
      第40回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 微弱電流による新規核酸iRedの細胞内送達と遺伝子発現制御2017

    • Author(s)
      小暮健太朗、藤川昂樹、Mahadi Hasan、濱 進、田中 保、田良島典子、南川典昭
    • Organizer
      遺伝子・デリバリー研究会第17回シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 微弱電流によるナノ粒子の皮内デリバリー2017

    • Author(s)
      小暮健太朗
    • Organizer
      第35回物性物理化学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Effective cellular delivery of intelligent shRNA expression device by faint electricity2017

    • Author(s)
      Kogure K, Tarashima N, Fujikawa K, Oshima Y, Torao T, Mimura M, Hasan M, Hama S, Tanaka T, Saito H, Minakawa N
    • Organizer
      6th FIP Pharmaceutical Sciences World Congress (PSWC)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transdermal delivery of liposomes encapsulating functional proteins by iontophoresis2017

    • Author(s)
      Kogure K, Kigasawa K, Hama S, Kajimoto K
    • Organizer
      ILS/LRD Liposome Advances Combined Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 微弱電流による核酸医薬の細胞内送達2017

    • Author(s)
      小暮健太朗、賀川真夕子、大島康史、虎尾 祐、三村美夕紀、福田達也、Hasan Mahadi、濱 進、田中 保
    • Organizer
      第26回DDSカンファランス
    • Related Report
      2017 Annual Research Report
  • [Presentation] 微弱電流処理による高分子医薬の細胞質送達と機能発現2017

    • Author(s)
      小暮健太朗、大島康史、虎尾 祐、三村美夕紀、藤川昂樹、Mahadi Hasan、濱 進、福田達也、田良島典子、田中 保、南川典昭
    • Organizer
      第39回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 微弱電流処理を利用した機能性核酸の細胞内取り込みの検討2017

    • Author(s)
      大島康史、Mahadi Hasan、田良島典子、濱 進、福田達也、田中 保、南川典昭、小暮健太朗
    • Organizer
      日本薬学会138年会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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