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Development of liposomal plastic antibody for novelDDS and applicaion for sepsis treatment

Research Project

Project/Area Number 16K15111
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

Oku Naoto  静岡県立大学, 薬学部, 教授 (10167322)

Co-Investigator(Kenkyū-buntansha) 浅井 知浩  静岡県立大学, 薬学部, 准教授 (00381731)
清水 広介  浜松医科大学, 学内共同利用施設等, 准教授 (30423841)
小出 裕之  静岡県立大学, 薬学部, 助教 (60729177)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsリポソーム / ノンインプリント人工抗体 / プラスチック抗体 / 敗血症 / ヒストン / 毒素の中和 / 膜流動性 / ポリマー粒子 / ポリマーリガンド / 毒素 / 中和活性 / 薬物送達 / 人工抗体 / 解毒
Outline of Final Research Achievements

Neutralization of toxins which entered into bloodstream, is important for curing several disorders. The gold standard to neutralize macromolecular toxins is antibodies, even though they have several problems such as high cost for preparation, and biological and chemical instability. On the other hand, plastic antibodies synthesized with monomers having appropriate functional groups may substitute with antibodies. Although they also have sereral problems such as short blood circulation time and not so high target-neutralizing activity.
By the way, decoration with polymer ligands (PLs) on liposomal membrane, enables appropriate interaction between PLs and target toxins through the lateral diffusion of PLs on the membrane. For obtaining the proof of concept, we used histones, major mediators of sepsis, as model toxins in the present study, and the results of our study suggested that abiotic PLs on the lipid nanoparticles can be useful for capturing and neutralizing target toxins.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results)

  • [Int'l Joint Research] University of California Irvine(U.S.A.)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Rational designing of an antidote nanoparticle decorated with abiotic polymer ligands for capturing and neutralizing target toxins.2017

    • Author(s)
      Koide H, Tsuchida H, Nakamoto M, Okishima A, Ariizumi S, Kiyokawa C, Asai T, Hoshino Y, Oku N
    • Journal Title

      J. Control. Release.

      Volume: 68 Pages: 335-342

    • DOI

      10.1016/j.jconrel.2017.10.028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A polymer nanoparticle with engineered affinity for a vascular endothelial growth factor (VEGF165)2017

    • Author(s)
      Hiroyuki Koide,Keiichi Yoshimatsu,Yu Hoshino,Shih-Hui Lee,Ai Okajima,Saki Ariizumi, Yudai Narita,Yusuke Yonamine,Adam C. Weisman,Yuri Nishimura,Naoto Oku,Yoshiko Miura,Kenneth J. Shea
    • Journal Title

      Nature Chemistry

      Volume: 9 Issue: 7 Pages: 715-722

    • DOI

      10.1038/nchem.2749

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] がん治療に向けたプラスチック人工抗体の開発2017

    • Author(s)
      小出裕之、有泉早紀、星野友、三浦佳子、Kenneth J. Shea、奥直人:
    • Organizer
      第81回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体内で標的生体高分子を吸着するPEG修飾ポリマーナノ粒子の設計2017

    • Author(s)
      林直希、小出裕之、有泉早紀、清川千秋、土田大貴、沖嶋杏奈、香門悠里、星野友、Kenneth J. Shea、奥直人
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] VEGFを吸着し中和する多官能性合成ポリマーナノ粒子を用いたがん治療2017

    • Author(s)
      小出裕之、有泉早紀、沖嶋杏奈、星野友、三浦佳子、Kenneth J. Shea、奥直人
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 標的高分子を吸着しその機能を中和する合成ポリマーナノ粒子の開発と難治性疾患治療への応用2017

    • Author(s)
      小出裕之
    • Organizer
      第11回QCM研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] VEGFと結合して中和する多官能性ポリマーナノ粒子の開発とがん治療へ応用2017

    • Author(s)
      小出裕之、有泉早紀、星野友、三浦佳子、シェアケネス、奥直人
    • Organizer
      第66回高分子討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症治療に向けたPEG含有ポリマーナノ粒子の開発2017

    • Author(s)
      林直希、小出裕之、沖島杏奈、星野友、シェアケネスジェイ、奥直人
    • Organizer
      第66回高分子討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of long-circulating polymer nanoparticles for sepsis treatment.2017

    • Author(s)
      N. Hayashi, H. Koide, A. Okishima, Y. Kamon, Y. Hoshino, K.J. Shea, N. Oku
    • Organizer
      American Association of Pharmaceutical Scientists Meeting and Exposition
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of polymer nanoparticles with affinity to a vascular endothlial growth factor for cancer therapy2017

    • Author(s)
      H. Koide, S. Ariizumi, Y. Hoshino, Y. Miura, S.J. Kenneth, N. Oku
    • Organizer
      American Association of Pharmaceutical Scientists Meeting and Exposition
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体内で標的毒素を中和するポリマーリガンド修飾脂質ナノ粒子の開発2016

    • Author(s)
      59.土田大貴、小出裕之、仲本正彦、沖嶋杏奈、有泉早紀、清川千秋、浅井知浩、星野 友、奥 直人
    • Organizer
      第38回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Multifunctional polymer-modified liposomes that capture and neutralize toxic protein, histones.2016

    • Author(s)
      48.Hiroki Tsuchida, Hiroyuki Koide, Masahiko Nakamoto, Anna Okishima, Saki Ariizumi, Chiaki Kiyokawa, Tomohiro Asai, Yu Hoshino, Naoto Oku
    • Organizer
      International Conference on Nanomedicine and Nanobiotechnoloty
    • Place of Presentation
      Paris, France
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 生体内で標的毒素を中和する脂質ナノ粒子解毒剤“Nano-dotes”の開発2016

    • Author(s)
      45.土田大貴、小出裕之、仲本正彦、沖嶋杏奈、有泉早紀、清川千秋、星野 友、奥 直人
    • Organizer
      第25回DDSカンファランス
    • Place of Presentation
      静岡
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] 生体内で標的毒素を中和する“リポソーム解毒剤”の開発2016

    • Author(s)
      43.土田大貴、小出裕之、仲本正彦、沖嶋杏奈、有泉早紀、清川千秋、星野 友、奥 直人
    • Organizer
      第10回QCM研究会
    • Place of Presentation
      東京
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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