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Inhibitory effects of supramolecular polyrotaxanes in inflammatory signaling and the application to the treatment of fulminant hepatitis

Research Project

Project/Area Number 18K19904
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Tamura Atsushi  東京医科歯科大学, 生体材料工学研究所, 准教授 (80631150)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsポリロタキサン / シクロデキストリン / コレステロール / 炎症 / Toll-like receptor / マクロファージ / 肝炎
Outline of Final Research Achievements

It is reported that cholesterol and its metabolites are involved in the inflammatory responses, and the cross-talk between sterols and immunological system has received increasing attention. In this study, the effects of β-cyclodextrin-threaded acid-degradable polyrotaxanes, which directly interact with intracellular cholesterols, on the inflammatory responses were explored. When the polyrotaxane-treated cells were stimulated with lipopolysaccharide, the inflammatory responses were remarkably inhibited accompanied by the reduction of intracellular free cholesterol content. Additionally, the polyrotaxanes suppressed the inflammatory responses in a mouse model of lipopolysaccharide-induced fulminant hepatitis. According to these results, it is expected that the polyrotaxanes would be applied for the treatment of various inflammatory diseases.

Academic Significance and Societal Importance of the Research Achievements

これまでにβ-シクロデキストリン含有ポリロタキサンによるコレステロール低下作用はニーマンピック病C型などのコレステロールの輸送障害が生じる疾患に対して有効であることが明らかとなっているが、本研究ではポリロタキサンによるコレステロールへの作用が細胞の炎症応答を抑制するという新たな知見を得た。また、急性炎症を引き起こしたマウスモデルでもポリロタキサンによる炎症応答抑制作用が確められた。詳細な作用機序についてはさらなる研究が必要であるが、炎症が原因となる疾患の治療に役立てることができると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] An antibody?supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded polyrotaxanes2020

    • Author(s)
      Nishida Kei、Tamura Astushi、Kang Tae Woong、Masuda Hiroki、Yui Nobuhiko
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 8 Issue: 31 Pages: 6975-6987

    • DOI

      10.1039/d0tb00575d

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrophobicity of acyl groups in α-cyclodextrin-threaded polyrotaxanes dominates the formation and stability of self-assembled nanoparticles2020

    • Author(s)
      Tonegawa Asato、Tamura Atsushi、Zhang Shunyao、Yui Nobuhiko
    • Journal Title

      Polymer

      Volume: 200 Pages: 122537-122537

    • DOI

      10.1016/j.polymer.2020.122537

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acetylation of Cyclodextrin‐Threaded Polyrotaxanes Yields Temperature‐Responsive Phase Transition and Coacervate Formation Properties2020

    • Author(s)
      Tonegawa Asato、Tamura Atsushi、Yui Nobuhiko
    • Journal Title

      Macromolecular Rapid Communications

      Volume: 41 Issue: 17 Pages: 2000322-2000322

    • DOI

      10.1002/marc.202000322

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellularly Degradable Polyrotaxanes for Therapeutic Applications2019

    • Author(s)
      Tamura Atsushi
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 2 Pages: 143-155

    • DOI

      10.1248/yakushi.18-00168-1

    • NAID

      130007587260

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-02-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design of supramolecular polymers for modulating intracellular lipids and their therapeutic applications2019

    • Author(s)
      Tamura Atsushi
    • Journal Title

      Drug Delivery System

      Volume: 34 Issue: 1 Pages: 62-63

    • DOI

      10.2745/dds.34.62

    • NAID

      130007636833

    • ISSN
      0913-5006, 1881-2732
    • Year and Date
      2019-01-25
    • Related Report
      2018 Research-status Report
    • Open Access
  • [Journal Article] Emerging Nanoassembly of Polyrotaxanes Comprising Acetylated α-Cyclodextrins and High-Molecular-Weight Axle Polymer2019

    • Author(s)
      Tonegawa Asato、Tamura Atsushi、Yui Nobuhiko
    • Journal Title

      ACS Macro Letters

      Volume: 8 Issue: 7 Pages: 826-834

    • DOI

      10.1021/acsmacrolett.9b00280

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced autophagy induction via the mitochondrial delivery of methylated β-cyclodextrin-threaded polyrotaxanes using a MITO-Porter2019

    • Author(s)
      Yamada Yuma、Daikuhara Shinnosuke、Tamura Atsushi、Nishida Kei、Yui Nobuhiko、Harashima Hideyoshi
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 50 Pages: 7203-7206

    • DOI

      10.1039/c9cc03272j

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mannosylated Polyrotaxanes for Increasing Cellular Uptake Efficiency in Macrophages through Receptor-Mediated Endocytosis2019

    • Author(s)
      Shibaguchi Kai、Tamura Atsushi、Terauchi Masahiko、Matsumura Mitsuaki、Miura Hiroyuki、Yui Nobuhiko
    • Journal Title

      Molecules

      Volume: 24 Issue: 3 Pages: 439-439

    • DOI

      10.3390/molecules24030439

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] オリゴエチレングリコール修飾ポリロタキサンによる炎症応答抑制効果2020

    • Author(s)
      大橋 萌, 田村篤志, 由井伸彦
    • Organizer
      第69回高分子学会年次大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Design of pH-responsive anionic polyrotaxanes and the modulation of cellular internalization efficiency2020

    • Author(s)
      Zhang Shunyao, 田村篤志, 由井伸彦
    • Organizer
      第69回高分子学会年次大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] シクロデキストリン超分子ポリマーを用いた疾患治療2019

    • Author(s)
      田村篤志
    • Organizer
      多糖の未来フォーラム2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] シクロデキストリン含有ポリロタキサンの医薬応用に関する研究2019

    • Author(s)
      田村篤志
    • Organizer
      第36回シクロデキストリンシンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Acid-degradable polyrotaxanes prevent LPS-induced fulminant hepatitis2019

    • Author(s)
      Atsushi Tamura, Nobuhiko Yui
    • Organizer
      Tissue Engineering & Regenerative Medicine International Society - AP Chapter and the 7th Asian Biomaterials Congress (TERMIS-AP + ABMC7 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞内分解性ポリロタキサンによる自然免疫系への介入2019

    • Author(s)
      田村篤志, 由井伸彦
    • Organizer
      第68回高分子討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] β-シクロデキストリン含有ポリロタキサンによる炎症抑制と急性肝炎治療への応用2019

    • Author(s)
      田村篤志, 大橋萌, 早川清雄, 大石由美子, 由井伸彦
    • Organizer
      第35回日本DDS学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 軸高分子組成の異なるポリロタキサンの合成と細胞に対する作用の評価2019

    • Author(s)
      長尾隆廣, 田村 篤志, 由井伸彦
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 炎症抑制を目指したマクロファージ標的指向性マンノース修飾ポリロタキサンの機能評価2018

    • Author(s)
      柴口塊, 田村篤志, 松村光明, 三浦宏之, 由井伸彦
    • Organizer
      日本補綴歯科学会 平成30年度東京支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞内分解性ポリロタキサンによるマクロファージの炎症応答抑制作用2018

    • Author(s)
      田村篤志, 大橋萌, 早川清雄, 大石由美子, 由井伸彦
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] マクロファージ標的型リガンド導入ポリロタキサンの構造特性が細胞内取込みへ及ぼす影響2018

    • Author(s)
      柴口塊, 田村篤志, 松井秀人, 松村光明, 三浦宏之, 由井伸彦
    • Organizer
      第67回高分子討論会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] カルボキシ化分解性ポリロタキサンの製造方法2020

    • Inventor(s)
      由井伸彦, 田村篤志, 張 順堯
    • Industrial Property Rights Holder
      国立大学法人 東京医科歯科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-082376
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] カルボキシ化分解性ポリロタキサン及びその製造方法2020

    • Inventor(s)
      由井伸彦、田村篤志、張順堯
    • Industrial Property Rights Holder
      由井伸彦、田村篤志、張順堯
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-082376
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2018-07-25   Modified: 2022-12-28  

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