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Development of Osteoporosis Treatment Nano-vehicles via Apoptotic Cell Inspired Materials

Research Project

Project/Area Number 19K19045
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57040:Regenerative dentistry and dental engineering-related
Research InstitutionTokyo Institute of Technology (2020-2021)
The University of Tokyo (2019)

Principal Investigator

Nakagawa Yasuhiro  東京工業大学, 物質理工学院, 助教 (90831264)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords骨粗鬆症 / IL2 / ホスファチジルセリン / アポトーシス細胞 / 免疫寛容 / 高分子ミセル / リウマチ / IL-2 / 免疫治療 / マテリアルセラピー
Outline of Research at the Start

関節リウマチ(RA)は近年よく見られる自己免疫疾患であり、発症部位での骨の粗鬆化に加え、全身性の骨粗鬆症を誘発する。RAでは炎症部位で産生される炎症性サイトカインが破骨細胞の分化成熟を誘導することで骨・関節の破壊が進行する。これらの炎症性サイトカインは血流によって全身に行き渡るため、RA発症部位以外での骨組織の粗鬆化が誘引される。これら炎症性サイトカイン産生・破骨細胞の分化誘導を担っているのは炎症性の発現型に分極したM1型マクロファージとTeff型のT細胞である。申請者はこれら免疫細胞に免疫寛容型であるM2型マクロファージとTreg型T細胞に誘導しうるナノメディシンを設計した。

Outline of Final Research Achievements

Rheumatoid arthritis (RA) is a common autoimmune disease that in recent years has been known to induce systemic osteoporosis. destruction of bones and joints progresses. In this study, we focused on the fact that apoptotic cells suppress the surrounding inflammatory environment through the exposure of phosphatidylserine, and devised a polymeric micellar mRNA carrier with anti-inflammatory activity. The apoptotic cell-mimetic polymer in the shell part induces the expression type of macrophages to M2 type and simultaneously delivers IL-2 production-inducing mRNA to macrophages.

Academic Significance and Societal Importance of the Research Achievements

高分子を利用した現在のドラッグデリバリーシステム(DDS)では、薬剤とキャリアに明確な役割分担がされており、高分子材料はキャリアとしてのみ使用されてきた。本研究では、薬剤を送達する高分子ミセルの外層に抗炎症機能を有するアポトーシス細胞模倣ポリマーを用いることにより、生理学的機能を持ったDDSキャリアの開発を目指すものである。
この機能性DDSキャリアを用いて、後期高齢化の進んだ日本においてニーズの高いリウマチ・骨粗鬆症治療法を構築することを目指す。

Report

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

    (45 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (35 results) (of which Int'l Joint Research: 13 results,  Invited: 1 results) Book (4 results)

  • [Journal Article] Microglial Immunoregulation by Apoptotic Cellular Membrane Mimetic Polymeric Particles2022

    • Author(s)
      Nakagawa Yasuhiro、Lee Jeonggyu、Liu Yihua、Abbasi Saed、Hong Taehun、Cabral Horacio、Uchida Satoshi、Ebara Mitsuhiro
    • Journal Title

      ACS Macro Letters

      Volume: 11 Issue: 2 Pages: 270-275

    • DOI

      10.1021/acsmacrolett.1c00643

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanically interlocked molecular architectures of valinomycin as cancer targeted prodrugs2022

    • Author(s)
      Tachihara Yoshihiro、Nakagawa Yasuhiro、Miyazaki Takuya、Anraku Yasutaka、Cabral Horacio
    • Journal Title

      Nano Select

      Volume: - Issue: 8 Pages: 1242-1251

    • DOI

      10.1002/nano.202100368

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of mechanically robust bilayer membranes of hydroxyapatite/collagen composites2021

    • Author(s)
      Irawan Vincent、Kajiwara Daichi、Nakagawa Yasuhiro、Ikoma Toshiyuki
    • Journal Title

      Materials Letters

      Volume: 291 Pages: 129514-129514

    • DOI

      10.1016/j.matlet.2021.129514

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recent advances in bioprinting technologies for engineering different cartilage-based tissues2021

    • Author(s)
      Agarwal Tarun、Chiesa Irene、Presutti Dario、Irawan Vincent、Vajanthri Kiran Yellappa、Costantini Marco、Nakagawa Yasuhiro、Tan Sheri-Ann、Makvandi Pooyan、Zare Ehsan Nazarzadeh、Sharifi Esmaeel、De Maria Carmelo、Ikoma Toshiyuki、Maiti Tapas Kumar
    • Journal Title

      Materials Science and Engineering: C

      Volume: 123 Pages: 112005-112005

    • DOI

      10.1016/j.msec.2021.112005

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanical anisotropy and fracture mode of binder jetting 3D printed calcium sulfate moldings2021

    • Author(s)
      Hamano Ryohei、Nakagawa Yasuhiro、Irawan Vincent、Ikoma Toshiyuki
    • Journal Title

      Applied Materials Today

      Volume: 25 Pages: 101160-101160

    • DOI

      10.1016/j.apmt.2021.101160

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PEG-Poly(1-Methyl-l-Tryptophan)-Based Polymeric Micelles as Enzymatically Activated Inhibitors of Indoleamine 2,3-Dioxygenase2019

    • Author(s)
      Huang George Lo、Tao Anqi、Miyazaki Takuya、Khan Thahomina、Hong Taehun、Nakagawa Yasuhiro、Cabral Horacio
    • Journal Title

      Nanomaterials

      Volume: 9 Issue: 5 Pages: 719-719

    • DOI

      10.3390/nano9050719

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 溶融冷却法による SrMg2(PO4)2: Eu(II)の単結晶作製と構造解析2022

    • Author(s)
      佐藤 耀敬, 中川 泰宏, 武田 博明, 生駒 俊之
    • Organizer
      日本セラミックス協会 2022年年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] グルコン酸カルシウムを用いた球状水酸アパタイト粒子の作製2022

    • Author(s)
      戸田 陽子, 中川 泰宏, 生駒 俊之
    • Organizer
      日本セラミックス協会 2022年年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 表面改質 NASICON 型リン酸ハフニウムの合成と放射線増感剤への応用2022

    • Author(s)
      中川 泰宏, 石栄 智貴, 生駒 俊之
    • Organizer
      日本セラミックス協会 2022年年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Characteristics of Hydroxyapatite Microparticles Bound with Virus Capture Polymer2022

    • Author(s)
      Yuhan Liu, Yasuhiro Nakagawa, Toshiyuki Ikoma
    • Organizer
      つくば医工連携フォーラム2022
    • Related Report
      2021 Annual Research Report
  • [Presentation] 光熱治療へむけた星形 Au-Ag ナノ粒子の形態と光応答性の評価2022

    • Author(s)
      會田 雄大, 中川 泰宏, 生駒 俊之
    • Organizer
      つくば医工連携フォーラム2022
    • Related Report
      2021 Annual Research Report
  • [Presentation] がんの放射線治療のための標的指向性リン酸ハフニウムナノ粒子の作製2022

    • Author(s)
      石栄 智貴, 中川 泰宏, 生駒 俊之
    • Organizer
      つくば医工連携フォーラム2022
    • Related Report
      2021 Annual Research Report
  • [Presentation] がんセラノスティクスに向けた Bi(III) /Eu(III) 置換水酸アパタイトナノ結晶の作製2022

    • Author(s)
      中川 泰宏, 松本 健太, 生駒 俊之
    • Organizer
      つくば医工連携フォーラム2022
    • Related Report
      2021 Annual Research Report
  • [Presentation] セラノスティクス実現に向けたBi(III)とEu(III)を置換した水酸アパタイトナノ結晶の作製2021

    • Author(s)
      中川 泰宏, 松本 健太, 生駒 俊之
    • Organizer
      第28回次世代医工学研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] セラノスティクス実現に向けたBi(III)とEu(III)を置換した水酸アパタイトナノ結晶の作製2021

    • Author(s)
      中川 泰宏, 松本 健太, 生駒 俊之
    • Organizer
      公益社団法人日本セラミックス協会 第34回秋季シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] アミノ基修飾した水酸アパタイトナノ結晶の合成2021

    • Author(s)
      古庄 陵真, 中川 泰宏, 生駒 俊之
    • Organizer
      公益社団法人日本セラミックス協会 第34回秋季シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Eu添加量によるSrMg2(PO4)2: Eu(II)の発光特性の変化2021

    • Author(s)
      佐藤 耀敬, 中川 泰宏, 生駒 俊之
    • Organizer
      公益社団法人日本セラミックス協会 第34回秋季シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] グルコン酸カルシウムを用いた中空アパタイト粒子の作製2021

    • Author(s)
      戸田 陽子, 中川 泰宏, 生駒 俊之
    • Organizer
      公益社団法人日本セラミックス協会 第34回秋季シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Gamma-ray Irradiation as a Novel Crosslinking Method for Collagen: A Study on Dose Dependent Effect for Collagen Membrane and its Crosslinking Mechanism2021

    • Author(s)
      Elenna Fariel, Yasuhiro Nakagawa, and Toshiyuki Ikoma
    • Organizer
      MATERIALS RESEARCH MEETING 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Preparation of Bi:Ln co-substituted Hydroxyapatite Nanocrystals via Hydrothermal Method for Cancer Theranostic ApplicationsPreparation of Bi:Ln co-substituted Hydroxyapatite Nanocrystals via Hydrothermal Method for Cancer Theranostic Applications2021

    • Author(s)
      Gerardo Martin III Quindoza, Yasuhiro Nakagawa, and Toshiyuki Ikoma
    • Organizer
      MATERIALS RESEARCH MEETING 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Application of silica-coated star-shaped Au-Ag nanoparticles modified with azo compounds to DDS2021

    • Author(s)
      Aida Yuta, Yasuhiro Nakagawa, and Toshiyuki Ikoma
    • Organizer
      MATERIALS RESEARCH MEETING 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Surface Engineered Bi(III) and Eu(III) Co doped Hydroxyapatite Nanocrystals for Cancer Theranostics2021

    • Author(s)
      Yasuhiro Nakagawa, Kenta Matsumoto, and Toshiyuki Ikoma.
    • Organizer
      MATERIALS RESEARCH MEETING 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bi(III) and Eu(III) Co-doped Hydroxyapatite Nanocrystals for Gamma-ray Based Cancer Theranostics2021

    • Author(s)
      Yasuhiro Nakagawa, Kenta Matsumoto, and Toshiyuki Ikoma.
    • Organizer
      第8回アジアバイオマテリアル学会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Strength improvement by alumina slurry impregnation method of alumina sintered body manufactured by 3D printer2021

    • Author(s)
      Naoto Sakimura, Ryohei Hamano, Yasuhiro Nakagawa, and Toshiyuki Ikoma
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanical properties of 3D printed alumina by slurry infiltration using metal ions2021

    • Author(s)
      Ryota Taguchi, Naoto Sakimura, Ryohei Hamano, Yasuhiro Nakagawa, and Toshiyuki Ikoma.
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Interfacial Interaction between Phosphate-Based Polymers and Silver-Hydroxyapatite Microparticles2021

    • Author(s)
      Yuhan Liu, Yasuhiro Nakagawa, and Toshiyuki Ikoma
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of hafnium phosphate compounds on cells in radiation therapy2021

    • Author(s)
      Tomoki Ishie, Yasuhiro Nakagawa, and Toshiyuki Ikoma.
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study on the Morphological Control of Silver Nanoparticles on the Surface of Hydroxyapatite Particles2021

    • Author(s)
      Yuta Aida, Yasuhiro Nakagawa, Masayuki Kyomoto, and Toshiyuki Ikoma.
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phosphorylcholine-installed polymers target pancreatic tumors through their exacerbated lipid metabolism2021

    • Author(s)
      Taehun Hong, Takuya Miyazaki, Kazunori Igarashi, Chen Pengwen, Keita Masuda, Yasuhiro Nakagawa, Yu Matsumoto, Tatsuya Yamasoba, and Horacio Cabral.
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis and characterization of Hydroxyapatite Hollow Nanoparticles for DNA Delivery Vehicles2021

    • Author(s)
      Yasuhiro Nakagawa, Sakurako Nishikori, Koji Moriya, Toshiaki Tanaka, and Toshiyuki Ikoma.
    • Organizer
      The Twelfth International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 難治性膵臓癌を標的としたホストゲスト相互作用を介した環状中分子担持型pH応答性高分子ミセルの開発2021

    • Author(s)
      Yoshihiro Tachihara, Yasuhiro Nakagawa, Anqi Tao, Huang George, Takuya Miyazaki, Kazunori Igarashi, Quader Sabina, 安楽 泰孝, 片岡 一則, Horacio Cabral
    • Organizer
      日本バイオマテリアル学会 2020 年度関東ブロック発表会
    • Related Report
      2020 Research-status Report
  • [Presentation] 放射線治療のためのリン酸ハフニウム化合物の合成2021

    • Author(s)
      石栄 智貴, 中川 泰宏, 生駒 俊之,
    • Organizer
      公益社団法人日本セラミックス協会 2021年年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Adsorption of Phosphate-Based Polymer on Silver-Hydroxyapatite Microparticles2021

    • Author(s)
      Yuhan Liu, Yasuhiro Nakagawa, Toshiyuki Ikoma
    • Organizer
      公益社団法人日本セラミックス協会 2021年年会
    • Related Report
      2020 Research-status Report
  • [Presentation] アゾ化合物を修飾したシリカ被覆星形Au - Agナノ粒子の作製2021

    • Author(s)
      會田 雄大, 中川 泰宏, 生駒 俊之,
    • Organizer
      公益社団法人日本セラミックス協会 2021年年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Building practical training in department of materials science and engineering through remote teaching2020

    • Author(s)
      Yuta Kurashina and Yasuhiro Nakagawa
    • Organizer
      Irago 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ホスホコリンを用いたミトコンドリアターゲティングリガンドの開発2020

    • Author(s)
      Taehun Hong, Takuya Miyazaki, Kazunori Igarashi, Yasuhiro Nakagawa, Eger Rigte BOONSTRA, Koji Kyoko, Yu Matsumoto, Tatsuya Yamasoba, Horacio Cabral.
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] アパタイト形成能をもつ 三次元造形アルミナ-生体活性ガラス-レジン複合体の作製2020

    • Author(s)
      浜野 凌平, 崎村 直登, 中川 泰宏, 生駒 俊之, 野崎 浩佑, 三浦 宏之,
    • Organizer
      6大学連携プロジェクト 第5回公開討論会
    • Related Report
      2020 Research-status Report
  • [Presentation] 核酸医薬の効率的送達を目指した中空水酸アパタイトナノ粒子の作製と評価2020

    • Author(s)
      中川 泰宏, 守矢 恒司, 田中 利明, 生駒 俊之,
    • Organizer
      MRM Forum 2020
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ホストゲスト相互作用を利用した環状化合物担持型pH応答性高分子ミセルの開発2020

    • Author(s)
      立原 義宏、宮崎 拓也、クォーダー サビナ、中川 泰宏、安楽 泰孝、片岡 一則、オラシオ カブラル
    • Organizer
      TEIJIN MIRAI FORUM 2020,
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of Polymeric Micelle-based Efficient Delivery System for Self-amplifying Replicon RNA2019

    • Author(s)
      Yasuhiro Nakagawa, Takuya Miyazaki, Federico Perche, Chantal Pichon, Horacio Cabra
    • Organizer
      第68回高分子年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ホストゲスト相互作用を介した環状化合物バリノマイシンの送達に向けたpH応答性高分子ミセルの開発2019

    • Author(s)
      立原 義宏、宮崎 拓也、クォーダー サビナ、中川 泰宏、安楽 泰孝、片岡 一則、オラシオ カブラル
    • Organizer
      第68回高分子年次大会
    • Related Report
      2019 Research-status Report
  • [Book] 糖応答型スマートポリマーを用いた人工レクチンの開発2020

    • Author(s)
      中川泰宏,荏原充宏
    • Total Pages
      8
    • Publisher
      シーエムシー出版
    • Related Report
      2020 Research-status Report
  • [Book] 非蛋白性合成レクチンを用いた糖認識バイオマテリアル2020

    • Author(s)
      中川泰宏,荏原充宏
    • Total Pages
      7
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2020 Research-status Report
  • [Book] 非蛋白性合成レクチンを用いた糖認識バイオマテリアル2019

    • Author(s)
      中川泰宏、荏原充宏
    • Total Pages
      7
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2019 Research-status Report
  • [Book] 抗炎症性を有する新たなバイオマテリアル開発2019

    • Author(s)
      中川泰宏、荏原充宏
    • Total Pages
      4
    • Publisher
      一般社団法人 日本人工臓器学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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