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Combined immunotherapy based on nano-DDS targeting tumor draining lymph nodes

Research Project

Project/Area Number 17H03974
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionHokkaido University

Principal Investigator

Nakamura Takashi  北海道大学, 薬学研究院, 助教 (20604458)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsドラッグデリバリーシステム / 脂質ナノ粒子 / がん免疫療法 / リンパ節 / siRNA / 薬物送達学 / がん免疫 / ナノテクノロジー / 制御性T細胞 / ドラッグデリバリー / 腫瘍所属リンパ節
Outline of Final Research Achievements

In this study, we obtained new insights: small-sized lipid nanoparticles showing excellent transability to the lymph node; negative charged lipid nanoparticles that are efficiently taken up by T cells in the lymph node; siRNA-loaded lipid nanoparticles showing effective gene silencing of IDO1, inhibitory gene, in dendritic cells; a strategy for reducing cytotoxicity of siRNA-loaded lipid nanoparticles in immune cells. In particular, we first reported the delivery to lymph node with lipid nanoparticles prepared by microfluidic devices. These findings should provide useful insights for the development of cancer immunotherapy based on lipid nanoparticles targeting lymph nodes.

Academic Significance and Societal Importance of the Research Achievements

マイクロ流路デバイスを用いて調製した脂質ナノ粒子のリンパ節移行性やリンパ節内分布を調べた報告はなく、今回の成果は非常に重要な知見である。また、微小サイズかつ負電荷の脂質ナノ粒子がリンパ節内のT細胞へ効率的に取り込まれるという知見は、T細胞を標的とした脂質ナノ粒子開発へと繋がる有用なものである。さらに、樹状細胞やヒト免疫細胞へのsiRNA送達を効率的かつ低毒性で実現する脂質ナノ粒子は、リンパ節内の抑制環境を制御するための技術として期待できる。

Report

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

    (18 results)

All 2020 2019 2018 2017 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (12 results) (of which Invited: 3 results) Remarks (1 results)

  • [Journal Article] The Effect of Size and Charge of Lipid Nanoparticles Prepared by Microfluidic Mixing on Their Lymph Node Transitivity and Distribution2020

    • Author(s)
      Nakamura Takashi, Kawai Minori, Sato Yusuke, Maeki Masatoshi, Tokeshi Manabu, Harashima Hideyoshi
    • Journal Title

      Molecular Pharmaceutics

      Volume: 17 Issue: 3 Pages: 944-953

    • DOI

      10.1021/acs.molpharmaceut.9b01182

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The silencing of indoleamine 2,3-dioxygenase 1 (IDO1) in dendritic cells by siRNA-loaded lipid nanoparticles enhances cell-based cancer immunotherapy2019

    • Author(s)
      Endo Rikito, Nakamura Takashi, Kawakami Kyoko, Sato Yusuke, Harashima Hideyoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 11335-11335

    • DOI

      10.1038/s41598-019-47799-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Innovative nanotechnologies for enhancing nucleic acids/gene therapy: Controlling intracellular trafficking to targeted biodistribution2019

    • Author(s)
      Nakamura Takashi, Yamada Yuma, Sato Yusuke, Khalil A Ikramy, Harashima Hideyoshi
    • Journal Title

      Biomaterials

      Volume: 218 Pages: 119329-119329

    • DOI

      10.1016/j.biomaterials.2019.119329

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Reducing the Cytotoxicity of Lipid Nanoparticles Associated with a Fusogenic Cationic Lipid in a Natural Killer Cell Line by Introducing a Polycation-Based siRNA Core2018

    • Author(s)
      Nakamura Takashi、Yamada Koharu、Fujiwara Yuki、Sato Yusuke、Harashima Hideyoshi
    • Journal Title

      Molecular Pharmaceutics

      Volume: 15 Issue: 6 Pages: 2142-2150

    • DOI

      10.1021/acs.molpharmaceut.7b01166

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integration of nano drug-delivery system with cancer immunotherapy2017

    • Author(s)
      Takashi Nakamura, Hideyoshi Harashima
    • Journal Title

      Therapeutic Delivery

      Volume: 8 Issue: 11 Pages: 987-1000

    • DOI

      10.4155/tde-2017-0071

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 脂質ナノ粒子のサイズと電荷がリンパ節移行とリンパ節内分布に与える影響2020

    • Author(s)
      中村孝司、河合美典、佐藤悠介、真栄城正寿、渡慶次学、原島秀吉
    • Organizer
      日本薬学会140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ナノDDS技術を利用したがん免疫療法の開発2019

    • Author(s)
      中村孝司
    • Organizer
      第35回 日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] siRNA搭載脂質ナノ粒子を用いた樹状細胞のIDO1発現制御と免疫細胞療法への展開2019

    • Author(s)
      遠藤力斗、中村孝司、川上今日子、佐藤悠介、原島秀吉
    • Organizer
      日本薬剤学会 第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] がん免疫療法のための核酸医薬DDS技術2019

    • Author(s)
      中村孝司
    • Organizer
      日本薬剤学会 第34年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] siRNA搭載脂質ナノ粒子を用いた免疫細胞の遺伝子発現制御2018

    • Author(s)
      中村孝司、黒井萌花、山田小春、藤原優希、藁科翔太、佐藤悠介、原島秀吉
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂質ナノ粒子を用いたヒトNK細胞株NK-92へのsiRNA導入2018

    • Author(s)
      中村孝司、山田小春、藤原優希、佐藤悠介、原島秀吉
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 微小化脂質ナノ粒子によるアジュバントのリンパ節送達2018

    • Author(s)
      中村孝司、河合美典、佐藤悠介、真栄城正寿、渡慶次学、原島秀吉
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] siRNA搭載脂質ナノ粒子を用いた樹状細胞のIDO発現抑制2018

    • Author(s)
      遠藤力斗、中村孝司、佐藤悠介、原島秀吉
    • Organizer
      日本薬学会北海道支部第145回例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリカチオンを用いたsiRNA搭載脂質ナノ粒子によるヒトNK細胞株への毒性の軽減2018

    • Author(s)
      山田小春、中村孝司、藤原優希、佐藤悠介、原島秀吉
    • Organizer
      日本薬学会北海道支部第145回例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂質ナノ粒子を基盤としたがん免疫療法のためのナノDDS開発2018

    • Author(s)
      中村孝司
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ヒトナチュラルキラー細胞株への毒性回避を目指したsiRNA搭載脂質ナノ粒子の開発2018

    • Author(s)
      山田小春、中村孝司、藤原優希、佐藤悠介、原島秀吉
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] リンパ節内樹状細胞を標的とした極小ナノキャリアシステムの開発2017

    • Author(s)
      河合美典、中村孝司、佐藤悠介、真栄城正寿、渡慶次学、原島秀吉
    • Organizer
      第33会日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 北海道大学大学院薬学研究院 薬剤分子設計学研究室ホームページ

    • URL

      http://www.pharm.hokudai.ac.jp/yakusetu/index.html

    • Related Report
      2019 Annual Research Report 2017 Annual Research Report

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

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