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Development of dual pH-responsive drug delivery career by the logical design of polymer

Research Project

Project/Area Number 15K18846
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionKeio University

Principal Investigator

Hiruta Yuki  慶應義塾大学, 薬学部(芝共立), 助教 (60710944)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords温度 / pH / 機能性高分子 / ミセル / DDS / 抗がん剤 / ナノ材料 / pH応答性ポリマー / 温度応答性ポリマー / ブロックコポリマー / ポリマーミセル / ドラッグデリバリー / ドキソルビシン / ドラッグデリバリーシステム / がん / ナノ
Outline of Final Research Achievements

We report a polymeric micelle drug delivery system, which enables selective intracellular uptake with external thermal stimulation, and effective release of a drug at internal acidic endosomal pH. We developed dual temperature- and pH-responsive polymeric micelle encapsulated anti-cancer agent, doxorubicin (DOX). The resultant micelle exhibited a temperature-dependent phase transition at a temperature slightly higher than body temperature, and intracellular uptake of encapsulated DOX was accelerated above phase transition temperature. The cytotoxicity of doxorubicin (DOX)-loaded dual temperature- and pH-responsive micelles against human cervical cancer HeLa cells was significantly greater at 42 °C than at 37 °C, This proof-of-concept synergistic two-step delivery system with enhanced intracellular uptake upon external thermal stimulation and rapid release of DOX at internal acidic endosomal pH was effective against tumor cells in vitro.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2017 2016 2015 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Int'l Joint Research: 9 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Design and synthesis of temperature-responsive polymer/silica hybrid nanoparticles and application to thermally controlled cellular uptake2017

    • Author(s)
      Yuki Hiruta, Ryo Nemoto, and Hideko Kanazawa
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 153 Pages: 2-9

    • DOI

      10.1016/j.colsurfb.2017.01.052

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Design of Environmentally Responsive Fluorescent Polymer Probes for Cellular Imaging2015

    • Author(s)
      Arisa Yamada, Yuki Hiruta, Jian Wang, Eri Ayano, Hideko Kanazawa
    • Journal Title

      Biomacromolecules

      Volume: 16 Issue: 8 Pages: 2356-2362

    • DOI

      10.1021/acs.biomac.5b00591

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 診断技術への応用を目指したスマートポリマープローブの精密設計2017

    • Author(s)
      蛭田勇樹
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Dual pH-resopnsive polymeric micelle for tumor cell selective uptake of anti-tumor agent2016

    • Author(s)
      Yuki Hiruta, Yuki Kanda, Atsushi Miki, Yuki Nagata, and Hideko Kanazawa
    • Organizer
      3rd International Conference on Biomaterials Science in Tokyo
    • Place of Presentation
      University of Tokyo, Japan
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] pH-Responsive Polymer Nanomedicine for Acidic tumor Targeting2016

    • Author(s)
      Yuki Hiruta, Yuki Nagata, Ryo Nemoto, and Hideko Kanazawa
    • Organizer
      International Nanomedicine Conference
    • Place of Presentation
      Hilton Mauritius Resorts & SPA, Flic-en-Flac, Mauritius
    • Year and Date
      2016-08-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Temperature-resopnsive fluorescence polymer nanoparticles with thermally controlled cellular uptakes2016

    • Author(s)
      Yuki Hiruta, Ryo Nemoto, Yuki Nagata, and Hideko Kanazawa
    • Organizer
      2016 CRS Annual Meeting & Exposition
    • Place of Presentation
      Washington State Convention Center, Seattle, USA
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tumor acidity sensitive polymeric micelle for selective cellular uptake of doxorubicin2016

    • Author(s)
      Yuki Hiruta, Yuki Nagata, Ryo Nemoto, and Hideko Kanazawa
    • Organizer
      2016 CRS Annual Meeting & Exposition
    • Place of Presentation
      Washington State Convention Center, Seattle, USA
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 固形がん選択的ターゲティングを目指したpH応答性ポリマーミセルの創製とpH選択的細胞取り込みの評価2016

    • Author(s)
      蛭田勇樹、永田勇貴、根本遼、金澤秀子
    • Organizer
      第32回日本DDS学会学術集会
    • Place of Presentation
      静岡県コンベンションツアーツセンター(静岡県・静岡市)
    • Year and Date
      2016-06-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 温度応答性ポリマーナノ粒子の創製と温度による細胞取り込み制御2016

    • Author(s)
      蛭田勇樹、根本遼、金澤秀子
    • Organizer
      第65回高分子学会年次大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県・神戸市)
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Temperature/pH-responsive Polymer Nanomaterials for Therapeutics and Diagnostics2016

    • Author(s)
      Yuki Hiruta, and Hideko Kanazawa
    • Organizer
      EMN Meeting on Hydrogel Materials
    • Place of Presentation
      Peninsula Excelsior Hotel, Singapore
    • Year and Date
      2016-05-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 温度応答性ポリマーナノ粒子の開発と温度応答性細胞取り込みの評価2016

    • Author(s)
      蛭田勇樹、小出さやか、根本遼、金澤秀子
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 固形がん選択的ターゲティングを目指したpH応答性高分子ミセルの創製2016

    • Author(s)
      永田勇貴、山田有紗、根本遼、蛭田勇樹、金澤秀子
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 温度応答性有機・無機ハイブリッドポリマーナノ粒子の開発2016

    • Author(s)
      蛭田勇樹、小出さやか、根本遼、金澤秀子
    • Organizer
      第25回インテリジェント材料/システムシンポジウム
    • Place of Presentation
      東京女子医科大学(東京都・新宿区)
    • Year and Date
      2016-01-08
    • Related Report
      2015 Research-status Report
  • [Presentation] がんの診断・治療を目指したpH応答性高分子の精密合成2016

    • Author(s)
      蛭田勇樹
    • Organizer
      第60回日本薬学会関東支部大会
    • Place of Presentation
      東京大学(東京都・文京区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] pH- and temperature-responsive organic-inorganic hybrid polymer nanoparticles with controlled cellular uptake2015

    • Author(s)
      Yuki Hiruta, Sayaka Koide, Jian Wang, Hideko Kanazawa
    • Organizer
      Pacifichem2015
    • Place of Presentation
      Oahu (USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of fluorescence probe for cellular imaging utilizing a temperature-responsive polymer2015

    • Author(s)
      Arisa Yamada, Jian Wang, Yuki Hiruta, Hideko Kanazawa
    • Organizer
      Pacifichem2015
    • Place of Presentation
      Oahu (USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preparation and characterization of thermo-responsive polymer modified liposomes aimed at application to anticancer agent delivery2015

    • Author(s)
      Ryo Nemoto, Jian Wang, Yuki Hiruta, Eri Ayano, Yoshie Maitani, Hideko Kanazawa
    • Organizer
      Pacifichem2015
    • Place of Presentation
      Oahu (USA)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Thermoresponsive Hybrid Nanoparticles Using Silica-block-copolymer2015

    • Author(s)
      Sayaka Koide, Jian Wang, Yuki Hiruta, Hideko Kanazawa
    • Organizer
      RSC Tokyo International Conference 2015
    • Place of Presentation
      Makuhari (Japan)
    • Year and Date
      2015-09-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 病態細胞の可視化を目指した温度・pH応答性蛍光ポリマープローブの開発2015

    • Author(s)
      蛭田勇樹、舟津孝明、王堅、小出さやか、金澤秀子
    • Organizer
      PPF2015
    • Place of Presentation
      長崎ホテル清風(長崎県・長崎市)
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
  • [Presentation] シリカブロックコポリマーを用いた温度応答型ハイブリット蛍光なの粒子の開発2015

    • Author(s)
      小出さやか、王堅、蛭田勇樹、金澤秀子
    • Organizer
      第75回分析化学討論会
    • Place of Presentation
      山梨大学(山梨県・山梨市)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

      http://keio-physchem.jp/index.html

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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