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Development of next-generation polymer-based nanoparticles and elucidating of their in vivo behavior

Research Project

Project/Area Number 19K15394
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 28030:Nanomaterials-related
Research InstitutionThe University of Kitakyushu

Principal Investigator

Fujii Shota  北九州市立大学, 環境技術研究所, 特任講師 (40794095)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsナノ粒子 / 生体適合性高分子 / 生体内動態 / 高分子鎖形態 / 高分子ナノ粒子 / コア架橋粒子 / ボトルブラシポリマー / 小角散乱 / 薬物送達システム / 高分子鎖密度 / ナノメディシン
Outline of Research at the Start

本研究では、生体内においてその構造を保持可能な高分子鎖含有コア架橋ナノ粒子(Furry Nanoballs: f-NBと命名)を利用し、それら粒子構造および高分子鎖形態を小角散乱法により詳細に理解したうえで、その粒子の体内動態を評価する。これにより、粒子表面の高分子鎖の種類だけでなく、高分子鎖形態およびナノ粒子形態と体内動態の相関性について新たな知見を得ることができる。また得られた結果から、体内動態を制御した上で薬理効果を発揮可能な高分子系ナノ粒子の設計指針を提案する。

Outline of Final Research Achievements

The purpose of this study was to design of structurally stable nanoparticles that do not rely on self-assembly such as micelles and to elucidate the correlation between their particle structure and in vivo behavior. We have developed core-crosslinked particles and molecular bottlebrush-based nanoparticles as the structurally stable nanoparticles. We have succeeded in developing a technique to control their nanoparticle structure including size, shape, and polymer chain conformations. In addition, the relationship between the polymer chain density on the particle surface and the in vivo fate of the nanoparticle as well as their drug release behavior was clarified. From the results of this research, we established a guideline for the design of nanoparticles in drug delivery systems using nanoparticles, which have attracted attention in the biotechnology field.

Academic Significance and Societal Importance of the Research Achievements

ナノ粒子を利用した薬剤送達システムの開発が急務の中、未だに応用に至った薬剤の開発には大きな障壁がある。その最大の原因として、ナノ粒子が生体内において迅速にクリアランスされてしまうことが挙げられる。本研究により、ナノ粒子構造とこのクリアランスの相関関係を解明することができた。この成果により、薬剤送達システムにおけるナノ粒子設計指針を確立することができ、これからの薬剤開発に大きく貢献されることが期待される。

Report

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

    (27 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 15 results) Presentation (10 results) (of which Int'l Joint Research: 7 results) Book (1 results)

  • [Int'l Joint Research] ANSTO(オーストラリア)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Impact of Zwitterionic Polymers on the Tumor Permeability of Molecular Bottlebrush-Based Nanoparticles2022

    • Author(s)
      Fujii Shota、Takano Shin、Nakazawa Kohji、Sakurai Kazuo
    • Journal Title

      Biomacromolecules

      Volume: in press Issue: 7 Pages: 2846-2855

    • DOI

      10.1021/acs.biomac.2c00216

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Internalization into cancer cells of zwitterionic amino acid polymers <i>via</i> amino acid transporter recognition2021

    • Author(s)
      Takano Shin、Sakurai Kazuo、Fujii Shota
    • Journal Title

      Polymer Chemistry

      Volume: 12 Issue: 42 Pages: 6083-6087

    • DOI

      10.1039/d1py01010g

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kinetically Controlling the Length of Self-Assembled Polymer Nanofibers Formed by Intermolecular Hydrogen Bonds2021

    • Author(s)
      Gruschwitz Franka V.、Klein Tobias、Kuchenbrod Maren T.、Moriyama Naoto、Fujii Shota、Nischang Ivo、Hoeppener Stephanie、Sakurai Kazuo、Schubert Ulrich S.、Brendel Johannes C.
    • Journal Title

      ACS Macro Letters

      Volume: 10 Issue: 7 Pages: 837-843

    • DOI

      10.1021/acsmacrolett.1c00296

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Polymer Micelles Composed of Molecular‐Bottlebrush‐Based Surfactants: Precisely Controlling Aggregation Number Corresponding to Polyhedral Structures2021

    • Author(s)
      Fujii Shota、Eichhorn Jonas、Schacher Felix H.、Brendel Johannes C.、Sakurai Kazuo
    • Journal Title

      Macromolecular Rapid Communications

      Volume: 42 Issue: 16 Pages: 2100285-2100285

    • DOI

      10.1002/marc.202100285

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural Analysis of an Octameric Resorcinarene Self-Assembly in Toluene and its Morphological Transition by Temperature2021

    • Author(s)
      Fujii Shota、Sakurai Kazuo
    • Journal Title

      The Journal of Physical Chemistry Letters

      Volume: 12 Issue: 28 Pages: 6464-6468

    • DOI

      10.1021/acs.jpclett.1c01978

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylcholine-Grafted Molecular Bottlebrush?Doxorubicin Conjugates: High Structural Stability, Long Circulation in Blood, and Efficient Anticancer Activity2020

    • Author(s)
      Takano Shin、Islam Waliul、Nakazawa Kohji、Maeda Hiroshi、Sakurai Kazuo、Fujii Shota
    • Journal Title

      Biomacromolecules

      Volume: 22 Issue: 3 Pages: 1186-1196

    • DOI

      10.1021/acs.biomac.0c01704

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Furry nanoparticles: synthesis and characterization of nanoemulsion-mediated core crosslinked nanoparticles and their robust stability in vivo2020

    • Author(s)
      Tanaka Rena、Arai Koichi、Matsuno Jun、Soejima Miyo、Lee Ji Ha、Takahashi Rintaro、Sakurai Kazuo、Fujii Shota
    • Journal Title

      Polymer Chemistry

      Volume: 11 Issue: 27 Pages: 4408-4416

    • DOI

      10.1039/d0py00610f

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anticancer efficacy of cyclodextrin-based hyperbranched polymer nanoparticles containing alpha-mangostin2020

    • Author(s)
      Doan Van T. H.、Takano Shin、Doan Ngoc Anh T.、Nguyen Phuong T. M.、Nguyen Van Anh T.、Pham Huong T. T.、Nakazawa Koji、Fujii Shota、Sakurai Kazuo
    • Journal Title

      Polymer Journal

      Volume: 53 Issue: 3 Pages: 481-492

    • DOI

      10.1038/s41428-020-00441-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Enhanced Binding Constant of Cyclodextrin to Alpha-mangostin in Hyperbranched Polymers2020

    • Author(s)
      Van Doan Thi Hong、Anh Doan Thi Ngoc、Fujii Shota、Sakurai Kazuo
    • Journal Title

      Chemistry Letters

      Volume: 49 Issue: 10 Pages: 1144-1146

    • DOI

      10.1246/cl.200210

    • NAID

      130007923149

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Monodisperse Micelles with Aggregation Numbers Related to Platonic Solids2020

    • Author(s)
      Lee Ji Ha、Fujii Shota、Takahashi Rintaro、Sakurai Kazuo
    • Journal Title

      Macromolecular Rapid Communications

      Volume: 41 Issue: 18 Pages: 2000227-2000227

    • DOI

      10.1002/marc.202000227

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterizing an siRNA-Containing Lipid-Nanoparticle Prepared by a Microfluidic Reactor: Small-Angle X-ray Scattering and Cryotransmission Electron Microscopic Studies2020

    • Author(s)
      Aburai Kenichi、Hatanaka Kentaro、Takano Shin、Fujii Shota、Sakurai Kazuo
    • Journal Title

      Langmuir

      Volume: 36 Issue: 42 Pages: 12545-12554

    • DOI

      10.1021/acs.langmuir.0c01079

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and characterization of nanoemulsion-mediated core crosslinked nanoparticles, and in vivo pharmacokinetics depending on the structural characteristics2020

    • Author(s)
      Matsuno Jun、Kanamaru Takuma、Arai Koichi、Tanaka Rena、Lee Ji Ha、Takahashi Rintaro、Sakurai Kazuo、Fujii Shota
    • Journal Title

      Journal of Controlled Release

      Volume: 324 Pages: 405-412

    • DOI

      10.1016/j.jconrel.2020.05.035

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural Polymorphism of Resorcinarene Assemblies2020

    • Author(s)
      Fujii Shota、Miyake Rika、Campo Liliana de、Lee Ji Ha、Takahashi Rintaro、Sakurai Kazuo
    • Journal Title

      Langmuir

      Volume: in press Issue: 22 Pages: 6222-6227

    • DOI

      10.1021/acs.langmuir.0c00861

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bundling Process of Citrulline Polypeptides upon UCST-Type Phase Separation2020

    • Author(s)
      Fujii Shota、Kuroyanagi Sotaro、Shimada Naohiko、Matsuno Jun、Lee Ji Ha、Takahashi Rintaro、Maruyama Atsushi、Sakurai Kazuo
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 124 Issue: 20 Pages: 4036-4043

    • DOI

      10.1021/acs.jpcb.0c00934

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cyclodextrin-based nanoparticles encapsulating α-mangostin and their drug release behavior: potential carriers of α-mangostin for cancer therapy2019

    • Author(s)
      Doan Van T. H.、Lee Ji Ha、Takahashi Rintaro、Nguyen Phuong T. M.、Nguyen Van Anh T.、Pham Huong T. T.、Fujii Shota、Sakurai Kazuo
    • Journal Title

      Polymer Journal

      Volume: 52 Issue: 4 Pages: 457-466

    • DOI

      10.1038/s41428-019-0296-y

    • NAID

      40022335569

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The effect of PEG molecular weight on the in vivo fate of PEGylated core cross-linked nanoparticles2022

    • Author(s)
      藤井翔太
    • Organizer
      ACS Spring 2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ボトルブラシ型高分子界面活性剤を用いたプラトニックミセルの構築2021

    • Author(s)
      藤井颯太
    • Organizer
      第70回高分子学会年次大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ボトルブラシポリマーから成る高分子ナノ粒子の腫瘍組織浸透性2021

    • Author(s)
      藤井翔太
    • Organizer
      第37回DDS学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生体適合性高分子ナノ粒子のがん細胞スフェロイドへの浸透挙動2021

    • Author(s)
      藤井翔太
    • Organizer
      第43回日本バイオマテリアル学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Tumor permeability of molecular bottlebrushes composed of polyelectrolytes2021

    • Author(s)
      藤井翔太
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Furry nanoparticles: cross-linked nanoparticles prepared via nanoemulsions and their robust stability in vivo2020

    • Author(s)
      Shota Fujii
    • Organizer
      259rd American Chemical Society NATIONAL MEETING & EXPOSITION
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Furry nanoparticles: Synthesis and characterization of nanoemulsion-mediated core crosslinked nanoparticles and their robust stability in vivo2020

    • Author(s)
      Shota Fujii
    • Organizer
      260rd American Chemical Society NATIONAL MEETING & EXPOSITION
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Constructing monodispese polymer micelles based on the concept of Platonic micelle2020

    • Author(s)
      Shota Fujii
    • Organizer
      ACIS2021: The 10th Australian Colloid and Interface Symposium
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Furry Nanoballs Bearing D4H/D4V Silicone: Synthesis, Structural Characterization, and Their Robust Stability in vivo2019

    • Author(s)
      Jun Matsuno
    • Organizer
      258rd American Chemical Society NATIONAL MEETING & EXPOSITION
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural Analysis of Resorcinarene Assemblies and Their Unique Aggregation Numbers Corresponding to Platonic Structures2019

    • Author(s)
      Shota Fujii
    • Organizer
      258rd American Chemical Society NATIONAL MEETING & EXPOSITION
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] Molecular Assemblies: Characterization and Applications2020

    • Author(s)
      Shota Fujii, Ji Ha Lee, Kazuo Sakurai
    • Total Pages
      13
    • Publisher
      ACS publications
    • Related Report
      2020 Research-status Report

URL: 

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

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