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Development of new therapy for lung-metastasis cancer by selecitve siRNA delivery to vasculature

Research Project

Project/Area Number 18K18351
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionChiba University

Principal Investigator

Sakurai Yu  千葉大学, 大学院薬学研究院, 特任助教 (00707234)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordssiRNA / 脂質ナノ粒子 / 肺転移 / 免疫チェックポイント阻害剤 / 肺転移がん / siRNA / がん / 転移
Outline of Final Research Achievements

In this study, we aimed at a development of new therapy for lung-metastatic cancer by siRNA delivery to tumor vasculature. Lung-metastasis model was prepared by an injection of murine cancer cells via the tail vein. When TET-MEND was administered into the lung-metastasis model, we observed a suppression of target protein in the metastasis. Then, to prove the therapeutic effect of TET-MEND, siRNA against delta-like ligand 4 (DLL4) was encapsulated into TET-MEND. Tumor volume was monitored after the continuous injection of TET-MEND encapsulating siRNA-DLL4. As a consequence, a significant prolongation in overall survival was obtained.

Academic Significance and Societal Importance of the Research Achievements

本成果は、既存のがんそのものを狙う治療法とは異なる新しい治療概念を提唱する。がんそのものを狙う治療法ではがんの増殖性に着目した医薬品が多い。そのため、正常な組織の増殖が盛んな毛髪組織や骨髄の免疫細胞にまで障害がおよび副作用の原因となる。一方で、本研究により確立した血管を標的とする治療法はがん細胞を標的としないためにその懸念は小さい。また、この両方が肺転移がんにも応用可能であることを示した。現在、転移したがんに対して有効な治療法は存在しないことから、ステージ後期のがんに苦しめられているがん患者に新たな選択肢を提供できるような治療法の開発に繋がりうる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Involvement of Caveolin-1-mediated transcytosis in the intratumoral accumulation of liposomes.2020

    • Author(s)
      Sakurai Y, Kato A, Harashima H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 525 Issue: 2 Pages: 313-318

    • DOI

      10.1016/j.bbrc.2020.02.086

    • NAID

      120007032614

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved Stability of siRNA-Loaded Lipid Nanoparticles Prepared with a PEG-Monoacyl Fatty Acid Facilitates Ligand-Mediated siRNA Delivery2020

    • Author(s)
      Sakurai, Y., Mizumura, W., Ito, K., Iwasaki, K., Katoh, T., Goto, Y., Suga, H., Harashima, H.
    • Journal Title

      Mol Pharm

      Volume: 17 Issue: 4 Pages: 1397-1404

    • DOI

      10.1021/acs.molpharmaceut.0c00087

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic enhancement of cellular uptake with CD44-expressing malignant pleural mesothelioma by combining cationic liposome and hyaluronic acid-lipid conjugate2019

    • Author(s)
      Sakurai Y., Kato A., Hida Y., Hamada J., Maishi N., Hida K., Harashima H
    • Journal Title

      J Pharm Sci

      Volume: 108 Issue: 10 Pages: 3218-3224

    • DOI

      10.1016/j.xphs.2019.06.012

    • NAID

      120006941697

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effective Therapy Using a Liposomal siRNA that Targets the Tumor Vasculature in a Model Murine Breast Cancer with Lung Metastasis.2018

    • Author(s)
      Sakurai Y, Hada T, Kato A, Hagino Y, Mizumura W, Harashima H.
    • Journal Title

      Mol Ther Oncolytics.

      Volume: 11 Pages: 102-108

    • DOI

      10.1016/j.omto.2018.10.004

    • NAID

      120006551598

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] サイズ・表面電化に基づく脂質ナノ粒子のリンパシステム内動態制御2019

    • Author(s)
      五味昌樹、櫻井遊、田中浩揮、三浦尚哉、秋田新介、山路佳久、三科信之、秋田英万.
    • Organizer
      第25回創剤フォーラム若手研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ビタミンE足場型pH応答性脂質用材料を基盤とするmRNAワクチンの開発2019

    • Author(s)
      大山遼太郎、館下菜穂、Jessica Anindita、田中浩揮、三浦尚也、櫻井遊、丹下耕太、中井悠太、吉岡宏樹、秋田英万.
    • Organizer
      第25回創剤フォーラム若手研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] リンパ管内皮細胞標的化siRNA搭載脂質ナノ粒子の開発2019

    • Author(s)
      阿部のどか、櫻井遊、小笠原諭、村田武士、丹下耕太、中井悠太、吉岡宏樹、玉川晋也、田中浩揮、秋田英万.
    • Organizer
      第25回創剤フォーラム若手研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 転移がんの血管を標的とするsiRNA封入脂質ナノ粒子を用いた治療法の開発2019

    • Author(s)
      櫻井遊、羽田智也、加藤月、萩野裕太、水村航、原島秀吉.
    • Organizer
      第25回創剤フォーラム若手研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of siRNA delivery system by EpCAM-targeting lipid nanoparticles using non-standard macrocyclic peptide.2018

    • Author(s)
      Yu Sakurai, Wataru Mizumura, Hideyoshi Harashima
    • Organizer
      the 29th Annual Meeting of the European Society for Biomaterials
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] センチネルリンパ節イメージング剤2020

    • Inventor(s)
      秋田英万,櫻井遊,田中浩揮,五味昌樹
    • Industrial Property Rights Holder
      国立大学法人 千葉大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-044942
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 届出時名称:新規ヒアルロン酸誘導体を含む薬剤キャリア及び、新規ヒアルロン酸誘導体とカチオン性脂質による薬剤送達方法2018

    • Inventor(s)
      加藤月、櫻井遊、原島秀吉、樋田京子、樋田泰浩、間石奈湖
    • Industrial Property Rights Holder
      加藤月、櫻井遊、原島秀吉、樋田京子、樋田泰浩、間石奈湖
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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