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Development of tumor-targetable, enzyme-specific activatable fluorescent probe for early diagnosis of tumor

Research Project

Project/Area Number 15K07896
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionHamamatsu University School of Medicine (2016-2017)
University of Shizuoka (2015)

Principal Investigator

Shimizu Kosuke  浜松医科大学, 光尖端医学教育研究センター, 准教授 (30423841)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsがんイメージング / リポソーム / アクチベータブル蛍光プローブ / マクロファージ / DDS / カテプシンB / ホスファチジルセリン / イメージング / がん / ターゲティング
Outline of Final Research Achievements

The aim of this study is to develop a novel near-infrared activatable fluorescent probe which enables to target macrophages in tumor tissues for early diagnosis of tumor. First, I synthesized an activatable fluorescent probe (P-ICG2) which show the near-infrared fluorescent property only after the lysosomal cathepsin B enzymatically cleaves the peptide chain in the probe. On the other hand, to deliver the probe to tumor tissue effectively, I also prepared PS-modified liposomes which can target macrophages infiltrating into tumor tissues. Then, I encapsulated P-ICG2 into the liposomes and developed a macrophage-targetable, enzyme-specific activatable fluorescent probe (P-ICG2-PS-Lip). P-ICG2-PS-Lip showed the fluorescence in lysosomes of mouse macrophage-like RAW264 cells after taking up into the cells. Furthermore, optical imaging of the solid tumor was succeeded, when P-ICG2-PS-Lip was intravenously injected to KLN205 tumor-bearing mouse and the fluorescence imaging was performed.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] Challenge to the development of diagnostic and therapeutic drugs using liposomal drug delivery systems:8<sup>th</sup> Young Scientist Award, Japan Society of DDS2016

    • Author(s)
      清水広介
    • Journal Title

      Drug Delivery System

      Volume: 31 Issue: 4 Pages: 352-360

    • DOI

      10.2745/dds.31.352

    • NAID

      130006846570

    • ISSN
      0913-5006, 1881-2732
    • Related Report
      2016 Research-status Report
    • Open Access / Acknowledgement Compliant
  • [Presentation] リポソームDDSの疾患診断・治療への応用2017

    • Author(s)
      清水広介
    • Organizer
      InnoPack Japanコンファレンス
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 光スイッチプローブDDSを応用した新規動脈硬化診断法の開発2017

    • Author(s)
      成田雄大、清水広介、間賀田泰寛、小川美香子、奥 直人
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マクロファージ標的化蛍光プローブによる動脈硬化不安定プラークの検出2017

    • Author(s)
      清水広介、成田雄大、Marten Maess、外村和也、間賀田泰寛、奥 直人、小川美香子
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 近赤外蛍光アクチベータブルプローブとマクロファージ標的化DDSによる動脈硬化不安定プラークイメージング2017

    • Author(s)
      成田雄大、清水広介、間賀田泰寛、外村和也、小川美香子、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] マクロファージ標的化アクチベータブル蛍光プローブによる動脈硬化不安定プラークの近赤外蛍光イメージング2017

    • Author(s)
      清水広介、成田雄大、Marten Maess、外村和也、間賀田泰寛、奥 直人、小川美香子
    • Organizer
      第12回日本分子イメージング学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 動脈硬化不安定プラークの近赤外蛍光イメージングを目的としたマクロファージ標的化リポソームの開発2017

    • Author(s)
      成田雄大、清水広介、間賀田泰寛、外村和也、小川美香子、奥 直人
    • Organizer
      第12回日本分子イメージング学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] アクチベータブル蛍光プローブDDS製剤による動脈硬化宇安定プラークイメージング2017

    • Author(s)
      成田雄大、清水広介、Maess Marten、間賀田泰寛、外村和也、小川美香子、奥 直人
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of enzyme-specific, macrophage-targeted near-infrared fluorescence probe for easy diagnosis of atherosclerosis2017

    • Author(s)
      Kosuke Shimizu, Yudai Narita, Marten Maess, Yasuhiro Magata, Mikako Ogawa, Naoto Oku
    • Organizer
      Controlled Release Society 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NIRF imaging vulnerable atherosclerotic plaques with activatable probe-encapsulated liposomes2017

    • Author(s)
      Yudai Narita, Kosuke Shimizu, Marten Maess, Kazuya Hokamura, Yasuhiro Magata, Mikako Ogawa, Naoto Oku
    • Organizer
      ILS and LRD Combined Conference 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NIRF imaging of atherosclerotic plaques with fluorescence activatable probe and macrophage-targeting DDS2017

    • Author(s)
      Yudai Narita, Kosuke Shimizu, Marten Maess, Kazuya Hokamura, Yasuhiro Magata, Mikako Ogawa, Naoto Oku
    • Organizer
      2017 AAPS Annual Meeting and Exposition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Optical imaging for detecting atherosclerotic plaques by use of macrophage-targeted liposomes encapsulating activatable fluorescent probe2017

    • Author(s)
      Kosuke Shimizu, Yudai Narita, Mikako Ogawa, Naoto Oku, Yasuhiro Magata
    • Organizer
      第22回静岡健康・長寿学術フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 動脈硬化不安定プラーク近赤外蛍光イメージングを指向したマクロファージ標的化DDS製剤の開発2016

    • Author(s)
      成田雄大、清水広介、小川美香子、Marten Maess、間賀田泰寛、奥 直人
    • Organizer
      日本分子イメージング学会第11回総会・学術集会
    • Place of Presentation
      神戸
    • Related Report
      2016 Research-status Report
  • [Presentation] リポソームDDSの魅力、疾患診断・治療へのチャレンジ2016

    • Author(s)
      清水広介
    • Organizer
      第32回日本DDS学会学術集会
    • Place of Presentation
      静岡
    • Related Report
      2016 Research-status Report
  • [Presentation] リポソームDDSの応用による疾患イメージング研究2015

    • Author(s)
      清水広介
    • Organizer
      日本分析化学会中部支部静岡講演会
    • Place of Presentation
      静岡
    • Year and Date
      2015-09-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] リポソームDDSを利用した疾患イメージング2015

    • Author(s)
      清水広介
    • Organizer
      第 15 回放射性医薬品・画像診断薬研究会
    • Place of Presentation
      京都
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Development of activatable fluorescence probe for easy diagnosis of cancer2015

    • Author(s)
      Yudai Narita, Yoshihito Takeuchi, Keisuke Ikemoto, Kosuke Shimizu, Mikako Ogawa, Yasuhiro Magata, Naoto Oku
    • Organizer
      42nd Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Edinburgh, Scotland
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] がん特異的検出を目指した蛍光スイッチ機能を有するリポソームの開発2015

    • Author(s)
      清水広介、成田雄大、橋本正寛、Marten Maess、小川美香子、間賀田泰寛、奥 直人
    • Organizer
      第10回日本分子イメージング学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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