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Nucleic acid-loaded polymeric micelle having a optimized hydrophobic layer toward optic nerve recovery via instillation

Research Project

Project/Area Number 18K18392
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionTokyo University of Science

Principal Investigator

Shigehito Osawa  東京理科大学, 理学部第一部応用化学科, 助教 (30780663)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords温度応答性 / 核酸キャリア / ポリオキサゾリン / ポリイオン会合体 / 点眼 / 眼内投与 / 核酸デリバリー / 核酸送達 / 点眼剤 / 高分子 / コロイド粒子 / 刺激応答性 / 高分子材料 / ドラッグデリバリーシステム
Outline of Final Research Achievements

We tried to develop novel eye drop medicine for retinal diseases.Herein, nanoparticles were prepared to have a nucleic acid component that produces therapeutic proteins in eye tissue and a hydrophobic component to avoid rapid elimination by tears after instillation. As a result of instilling the prepared particles into eyes of mice, the expected protein production was not observed, but high protein expression was observed when administered intraocularly. In order to enhance the effect as an eye drop medicine, it would be required to increase the hydrophobicity of the nanoparticles or to utilize other interactions between the nanoparticles and cell surface to enhance the transfer of the therapeutic nucleic acids into the eye.

Academic Significance and Societal Importance of the Research Achievements

核酸は細胞に取り込まれた後、タンパク発現を制御するため医薬としての利用が注目されている。核酸の細胞内あるいは組織内移行量を高めて効能をあげる工夫として、ナノ粒子化、疎水性部位の導入が広く研究されている。しかし今回試行した点眼剤による眼組織への核酸導入においては、ナノ粒子としての形態を維持できる範囲での疎水性部導入では、期待通りのタンパク発現が得られなかった。眼は特にバリア性の高い組織で、核酸を眼内に移行させるキャリア設計には疎水性がもっと高くする(場合によってはナノ粒子としての形態にこだわらない)、あるいは他の相互作用も合わせて利用する必要性が示唆された。

Report

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

    (13 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Installation of a Thermoswitchable Hydrophobic Domain into a Unimer Polyion Complex for Enhanced Cellular Uptake of siRNA2020

    • Author(s)
      Kim Beob Soo、Osawa Shigehito、Yum Jongmin、Naito Mitsuru、Miyata Kanjiro
    • Journal Title

      Bioconjugate Chemistry

      Volume: 31 Issue: 5 Pages: 1320-1326

    • DOI

      10.1021/acs.bioconjchem.0c00238

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increase in the apparent intercalation ability of a platinum complex via multivalency by installation into the sidechain of a graft copolymer and observation of structural changes in the intercalated DNA2019

    • Author(s)
      Osawa Shigehito、Takahashi Riichi、Watanabe Remi、Kubo Sayaka、Otsuka Hidenori
    • Journal Title

      RSC Advances

      Volume: 9 Issue: 45 Pages: 26429-26434

    • DOI

      10.1039/c9ra03485d

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] N-Hydroxysuccinimide Bifunctionalized Triblock Cross-Linker Having Hydrolysis Property for a Biodegradable and Injectable Hydrogel System2019

    • Author(s)
      Ishikawa Shohei、Matsukuma Daisuke、Iijima Kazutoshi、Iijima Michihiro、Osawa Shigehito、Otsuka Hidenori
    • Journal Title

      ACS Biomaterials Science & Engineering

      Volume: 印刷中 Issue: 11 Pages: 5759-5769

    • DOI

      10.1021/acsbiomaterials.9b00218

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 金属錯体を含むグラフトコポリマーの合成とバイオマテリアルへの展開2020

    • Author(s)
      大澤重仁、大塚英典
    • Organizer
      第69回高分子年次大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Random copolymer grafting oligo (ethylene glycol)s and zinc complexes with dipicolylamine to design polyplex loading plasmid DNA toward gene delivery2019

    • Author(s)
      Sayaka Kubo, Shigehito Osawa, and Hidenori Otsuka
    • Organizer
      OKINAWA COLLOIDS 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ジピコリルアミン亜鉛錯体とオリゴエチレングリコールをグラフトした高分子鎖の合成と遺伝子キャリアとしての機能評価2019

    • Author(s)
      久保明香、黒川颯介、大澤重仁、大塚英典
    • Organizer
      第9回CSJ化学フェスタ
    • Related Report
      2019 Annual Research Report
  • [Presentation] ジピコリルアミン亜鉛錯体とOEGユニットを含むメタクリル酸ベースのランダム共重合体の合成と遺伝子キャリアとしての機能評価2019

    • Author(s)
      久保明香、黒川颯介、大澤重仁、大塚英典
    • Organizer
      第68回高分子年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Messenger RNA loaded polyplex micelles having hydrophobic core protective layer composed of thermo-switchable poly(oxazoline) for promoted gene expression2019

    • Author(s)
      Shigehito Osawa, Kensuke Osada, and Kazunori Kataoka
    • Organizer
      ACS Spring 2019 National Meeting & Exposition
    • Related Report
      2019 Annual Research Report
  • [Presentation] Messenger RNA loaded polyplex micelles having hydrophobic core protective layer composed of thermo-switchable poly(oxazoline) for promoted gene expression2019

    • Author(s)
      Shigehito Osawa, Kensuke Osada, Kazunori Kataoka
    • Organizer
      ACS Spring 2019 National Meeting & Exposition
    • Related Report
      2018 Research-status Report
  • [Presentation] Accelerated polymerization of dipicolylamine acrylate monomer via pre-formation of the monomer metal complex2018

    • Author(s)
      Sosuke Kurokawa, Shigehito Osawa, Hidenori Otsuka
    • Organizer
      1st G'L'owing Polymer Symposium in KANTO
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased apparent DNA intercalation property of platinum metal complex by constructing comb-type polymer2018

    • Author(s)
      Shigehito Osawa, Riichi Takahashi, Hidenori Otsuka
    • Organizer
      1st G'L'owing Polymer Symposium in KANTO
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 温度応答性ポリオキサゾリン鎖からなる疎水性保護層を有する核酸内包高分子ミセル2018

    • Author(s)
      大澤重仁、長田健介、大塚英典、片岡一則
    • Organizer
      第28回バイオ・高分子シンポジウム
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 高分子金属錯体及びその製造方法2018

    • Inventor(s)
      大澤重仁、黒川颯介
    • Industrial Property Rights Holder
      大澤重仁、黒川颯介
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-230395
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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