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Clarification of macrophage specificity using endocytosis typing for theraputic control of disease

Research Project

Project/Area Number 19K22534
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionYamaguchi University

Principal Investigator

Nakamura Michihiro  山口大学, 大学院医学系研究科, 教授 (10314858)

Co-Investigator(Kenkyū-buntansha) 中村 純奈  山口大学, 大学院医学系研究科, 助教 (10821944)
望月 ちひろ  山口大学, 大学院医学系研究科, 助教 (80831875)
西尾 忠  山口大学, 大学院医学系研究科, 助教 (80401892)
加藤 茂樹  山口大学, 大学院医学系研究科, 助教 (90790767)
KIM HYUNGJIN  山口大学, 大学院医学系研究科, 助教 (80711457)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywordsマクロファージ / 有機シリカ粒子 / エンドサイトーシス / タイピング / 特異性 / ナノ粒子 / ナノ医学 / 有機シリカナノ粒子
Outline of Research at the Start

マクロファージ(Mφ)は生体のすべての組織に存在する免疫細胞で、生体に侵入した様々な異物や病原体などを認識し、エンドサイトーシスにより取込んで処理する。現在、Mφは疾患関連Mφ等の多様性やタイピングの議論が活発化しているが、現在のタイピングの方法には限界があり、新たなアプローチが必要とされている。我々は独自の多機能粒子作製技術を駆使しMφのエンドサイトーシスを多角的に検討することでタイピングし、Mφの多様性の解明を進めると共に特異性へと変革することに挑戦する。本研究はMφが関連する感染症やがん、成人病に対してMφ特異性の解明による革新的医療の実現が最終的な目的である。

Outline of Final Research Achievements

Macrophages (Mφ) are immune cells that exist in all tissues of the living body, recognize various foreign substances and pathogens that have invaded the living body, and uptake and process them by endocytosis. Mφ is important for maintaining homeostasis and immunity of the our body and is also involved in the pathology. We wiil challenge to clarify the "diversity" of Mφ and transform it into "specificity, based on endocytosis typing using our multi-functional organosilica nanoparticle technology. We will identify specific Mφ involved in immune mechanisms such as infection, and disease-specific Mφ. We will control them to cure patients. Our ultimate goal of this study is to realize innovative medicine based on clarification of Mφ-specificity for infectious diseases, cancers, and adult diseases related to Mφ.

Academic Significance and Societal Importance of the Research Achievements

現在、医薬として抗体が活用されているが、当初は多様性の議論に始まり、遺伝子解析による多様性の解明、そして遺伝子工学による抗体医薬の開発につながり医学に大きな貢献を果たした。現在、Mφは多様性の議論が活発化している段階にある。本研究はMφの多様性の概念を特異性へと大きく変革するものである。エンドサイトーシス・タイピングによる特異性のメカニズムの解明は関連する因子の同定、さらにそれらを制御する分子の創生へと展開し、治療薬の開発に繋がる。さらに特異的Mφの機能制御によりMφ自体を治療用細胞として応用できる。本研究はMφ特異性を基盤とした革新的な医療の創成に挑戦するものであり、大きな意義を持つ。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (34 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (20 results) (of which Int'l Joint Research: 11 results,  Invited: 7 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] City of Hope/University of California, Los Angeles(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Sohag University(エジプト)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] City of Hope/University of California, Los Angeles(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of California, Los Angeles/City of Hope/University of South California(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Au(I)チオラート錯体含有発光チオール有機シリカナノ粒子の合成と蛍光顕微鏡イメージングへの応用2022

    • Author(s)
      望月 ちひろ・中村 純奈・中村 教泰
    • Journal Title

      The Bulletin of the Nano Science and Technology (ナノ学会刊行和文誌)

      Volume: 2 Pages: 53-57

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Photostable and Biocompatible Luminescent Thiol-Terminated Organosilica Nanoparticles with Embedded Au(I)-Thiolate Complexes for Fluorescent Microscopic Imaging2021

    • Author(s)
      Mochizuki Chihiro、Nakamura Junna、Nakamura Michihiro
    • Journal Title

      ACS Applied Nano Materials

      Volume: 4 Issue: 12 Pages: 13305-13318

    • DOI

      10.1021/acsanm.1c02826

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Size-dependent biodistribution of thiol-organosilica nanoparticles and F4/80 protein expression in the genital tract of female mice after intravaginal administration2021

    • Author(s)
      Awaad Aziz、Nakamura Michihiro
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 155 Issue: 6 Pages: 683-698

    • DOI

      10.1007/s00418-021-01974-1

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Protein corona components of polyethylene glycol-conjugated organosilica nanoparticles modulates macrophage uptake2021

    • Author(s)
      Kim Hyungjin、Roth Daniel、Isoe Yasuhiro、Hayashi Koichiro、Mochizuki Chihiro、Kalkum Markus、Nakamura Michihiro
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 199 Pages: 111527-111527

    • DOI

      10.1016/j.colsurfb.2020.111527

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of Non-Porous Silica Nanoparticles towards Cancer Photo-Theranostics2021

    • Author(s)
      Mochizuki Chihiro、Nakamura Junna、Nakamura Michihiro
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 1 Pages: 73-73

    • DOI

      10.3390/biomedicines9010073

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Near-Infrared Fluorescent Thiol-Organosilica Nanoparticles That Are Functionalized with IR-820 and Their Applications for Long-Term Imaging of in Situ Labeled Cells and Depth-Dependent Tumor in Vivo Imaging2020

    • Author(s)
      Nakamura Michihiro、Hayashi Koichiro、Nakamura Junna、Mochizuki Chihiro、Murakami Takuya、Miki Hirokazu、Ozaki Shuji、Abe Masahiro
    • Journal Title

      Chemistry of Materials

      Volume: 32 Issue: 17 Pages: 7201-7214

    • DOI

      10.1021/acs.chemmater.0c01414

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between the glutathione-responsive degradability of thiol-organosilica nanoparticles and the chemical structures2019

    • Author(s)
      T. Doura, T. Nishio, F. Tamanoi, M. Nakamura
    • Journal Title

      J. Mater. Res.

      Volume: 34 Issue: 7 Pages: 1266

    • DOI

      10.1557/jmr.2018.501

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Au(I)錯体含有発光有機シリカナノ粒子の合成と細胞蛍光イメージングへの応用2022

    • Author(s)
      望月ちひろ, 中村純奈, 中村教泰
    • Organizer
      第127回日本解剖学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Au(I)錯体含有発光有機シリカナノ粒子の合成と蛍光イメージングへの応用2021

    • Author(s)
      望月 ちひろ, 中村純奈, 中村教泰
    • Organizer
      ナノ学会第19回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Size-dependent Distribution of Fluorescent Thiol-Organosilica Particles in the Mouse Popliteal Lymph Nodes2021

    • Author(s)
      Chika Kuroda, Michihiro Nakamura
    • Organizer
      The 8th Japan-China Symposium on Nanomedicine
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The synthesis of luminescence Au(I) complex-containing thiol-organosilica nanoparticles and their application for bioimaging2021

    • Author(s)
      中村教泰、中村純奈、望月 ちひろ
    • Organizer
      The 8th Japan-China Symposium on Nanomedicine
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multifunctionalized Organosilica Nanoparticles for Biomedical Application2021

    • Author(s)
      Michihiro Nakamura
    • Organizer
      The 8th Japan-China Symposium on Nanomedicine
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Organosilica Nanoparticles for Biomedical Applications toward Nano-Theranostics2021

    • Author(s)
      Michihiro Nakamura
    • Organizer
      2021 Spring Meeting of the European Materials Research Society (E-MRS) 「FRONTIER RESEARCH in BIOMATERIALS and NANOMEDICINE FORUM )」(VIRTUAL Conference)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ナノ医学・セラノスティクスの発展に向けて2021

    • Author(s)
      中村教泰
    • Organizer
      令和3年度 青藍会 総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Au(I)錯体含有発光有機シリカナノ粒子の合成と細胞蛍光イメージング2021

    • Author(s)
      望月 ちひろ, 中村純奈, 中村教泰
    • Organizer
      第75回中国・四国支部学術集会-日本解剖学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 蛍光有機シリカナノ粒子を用いた膝下リンパ節におけるサイズ依存的分布の解析2021

    • Author(s)
      黒田千佳, 望月 ちひろ, 中村純奈, 加藤茂樹, 中村教泰
    • Organizer
      第75回中国・四国支部学術集会-日本解剖学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] In Vivo Imaging using Multifunctional Organosilica Nanoparticles2021

    • Author(s)
      Michihiro Nakamura
    • Organizer
      14th International Symposium on Nanomedicine(ISNM2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The synthesis of luminescence Au(I) complex-containing thiol-organosilica nanoparticles their application for cell imaging2021

    • Author(s)
      Chihiro Mochizuki, Junna Nakamura, Michihiro Nakamura
    • Organizer
      14th International Symposium on Nanomedicine(ISNM2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Macrophage Specificity: Imaging and Characterization of Interaction between Macrophages and Fluorescent Organosilica Nanoparticles Depending on Surface Structure and Size2021

    • Author(s)
      Michihiro Nakamura, Junna Nakamura, Chihiro Mochizuki, Shigeki Kato
    • Organizer
      Cell Bio Virtual
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multifunctional organosilica nanoparticles for highly sensitive detection and imaging2021

    • Author(s)
      Michihiro Nakamura
    • Organizer
      Molecular Med Tri-Con Virtual Conference & Expo
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 有機シリカ近赤外線蛍光ナノ粒子による標識細胞の長期間in vivoイメージング2021

    • Author(s)
      中村教泰、中村純奈、望月 ちひろ
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Moodleを活用したラーニングアナリティクスによる学修行動と成績の関連性の評価2021

    • Author(s)
      中村 純奈, 望月 ちひろ, 金 亨振, 中村 教泰
    • Organizer
      第126回日本解剖学会総会・全国学術集会・第98回日本生理学会大会合同大会
    • Related Report
      2020 Research-status Report
  • [Presentation] マクロファージ特異性: 蛍光有機ナノシリカ粒子を用いたポリエチレングリコール耐性マクロファージの同定2020

    • Author(s)
      中村教泰
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 物質機能変換のためのナノ構造体としての 有機シリカナノ粒子2020

    • Author(s)
      中村 教泰
    • Organizer
      第二回ミニシンポジウム 生命科学と物質科学の融合
    • Related Report
      2019 Research-status Report
  • [Presentation] Organosilica Nanoparticles Toward Theranostic2019

    • Author(s)
      Michihiro Nakamura
    • Organizer
      7th China-Japan Symposium on Nanomedicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Biomedical Imaging using Multifunctional Organosilica Nanoparticles2019

    • Author(s)
      Michihiro Nakamura
    • Organizer
      13th International Symposium on Nanomedicine (ISNM2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Macrophage Specificity: Identification of Polyethylene Glycol-Resistant Macrophages on Stealth Imaging in Vitro Using Fluorescent Organosilica Nanoparticles2019

    • Author(s)
      Michihiro Nakamura
    • Organizer
      ASCB/EMBO Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 山口大学大学院医学系研究科 器官解剖学講座

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~nanomed1/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report
  • [Remarks] 国立大学法人山口大学ナノ・セラノスティクス国際センター

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~nanomed1/iNTC-index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report
  • [Patent(Industrial Property Rights)] 観察方法およびマーカー2022

    • Inventor(s)
      春田 知洋、中村 教泰
    • Industrial Property Rights Holder
      日本電子株式会社、山口大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-053918
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report

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Published: 2019-07-04   Modified: 2023-01-30  

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