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Molecular Design of Nanostructures with High-Density Nucleic Acid Brushes for Carrier-Free DDS

Research Project

Project/Area Number 17K05938
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionTokyo University of Science

Principal Investigator

AKIYAMA YOSHITSUGU  東京理科大学, 基礎工学部教養(長万部), 准教授 (40640842)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsキャリアフリーDDS / DNA密生層 / ナノ構造体 / コンビネーション治療 / ナノ医療 / 自己崩壊性高分子 / 核酸医薬 / 分子標的医薬 / 刺激応答性高分子 / ドラッグデリバリーシステム / ナノバイオマテリアル / 生体材料 / がん化学療法 / 遺伝子治療
Outline of Final Research Achievements

We developed spherical nucleic acids having a core structure of self-immolative polymer that can undergo disassembly through a self-immolative fragmentation. A poly(carbamate)(PC)derivative composed of 4-aminobenzyl alcohol as a repeat unit was treated with carbonyldiimidazole, followed by conjugation with DNA on a solid support to give a DNA-PC conjugate. Subsequent cleavage from the solid support and dialysis against water resulted in a self-assembly of DNA-PC conjugate with a narrow unimodal size distribution in DLS measurements, indicating formation of nanostructure covered with a dense DNA shell in aqueous solution. The nanostructure thus obtained may undergo domino-like disassembly of PC that can release 4-aminobenzyl alcohol at several triggers. More importantly, this methodology leads to the creation of carrier-free DDS by replacing each unit in the PC with a pharmaceutical drug having a 4-aminobenzyl alcohol substitution.

Academic Significance and Societal Importance of the Research Achievements

核酸密生層の内殻を自己崩壊性高分子とする試みは既往研究がなく、外部刺激に呼応した特異崩壊性の精密制御は、ナノ医療だけでなくナノ界面科学における基礎と応用の双方にとって興味がもたれる。また、内殻を金ナノ粒子としたハイブリッド型ナノ材料は低分子医薬の活性を目視で迅速に判定できる簡易スクリーニング技術に応用できる。今後、内殻を形成する低分子医薬オリゴマーを目視探索技術で選択し、キャリアフリー型ナノDDS製剤に組み込むことによって、治療用途に応じた異種医薬の候補探索から治療までを一体化したナノ医療の発展に広く貢献できるものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017 Other

All Journal Article (2 results) Presentation (19 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] 核酸を密生層としたナノ粒子設計とナノ診断・治療への応用2018

    • Author(s)
      秋山好嗣
    • Journal Title

      アグリバイオ

      Volume: 2 Pages: 57-56

    • NAID

      40021807698

    • Related Report
      2018 Research-status Report
  • [Journal Article] 核酸の密生層を活用するナノバイオ研究2018

    • Author(s)
      秋山好嗣
    • Journal Title

      BIO Clinica

      Volume: 33 Pages: 46-50

    • Related Report
      2017 Research-status Report
  • [Presentation] DNA密生型金ナノ粒子を用いたブレオマイシン誘導体の目視探索技術の開発2019

    • Author(s)
      木村和徳 秋山好嗣 宝田徹 前田瑞夫 菊池明彦
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNA二重鎖密生型金ナノ粒子を用いた抗がん剤の目視活性評価法の構築2019

    • Author(s)
      秋山好嗣 木村和徳 宝田徹 前田瑞夫 菊池明彦
    • Organizer
      日本分析化学会第68年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 内殻を自己崩壊性高分子としたDNA密生型ナノ構造体の作製2019

    • Author(s)
      福本汐音、川出茉実、木村和徳、秋山好嗣、菊池明彦
    • Organizer
      第68回高分子討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Simple colorimetric assay of anti tumor agents utilizing double-stranded DNA-modified gold nanoparticles2019

    • Author(s)
      Kazunori Kimura, Yoshitsugu Akiyama, Thru Takarada, Mizuo Maeda, Akihiko Kikuchi
    • Organizer
      Tissue Engineering and Regenerative Medicine International Society-AP Chapter and the 7th Asian Biomaterials Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA親和性抗がん剤の目視探索に向けたDNA密生型金ナノ粒子のマテリアル設計2019

    • Author(s)
      木村和徳 秋山好嗣 宝田徹 前田瑞夫 菊池明彦
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 自己崩壊性ポリ(カルバメート)ーDNAコンジュゲートの精密合成とDNA密生型ナノ構造体の調製2019

    • Author(s)
      福本汐音 川出茉実 木村和徳 秋山好嗣 菊池明彦
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Colorimetric assay of bleomycin-mediated DNA damage utilizing double-stranded DNA-functionalized gold nanoparticles2019

    • Author(s)
      Kazunori Kimura, Yoshitsugu Akiyama, Tohru Takarada, Mizuo Maeda, Akihiko Kikuchi
    • Organizer
      29th Annual Meeting of MRS-Japan 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] A Simple Colorimetric Assay of Bleomycin-Induced DNA Cleavage Utilizing Double-Stranded DNA-Modified Gold Nanoparticles2019

    • Author(s)
      Kazunori Kimura, Yoshitsugu Akiyama, Tohru Takarada, Mizuo Maeda,Akihiko Kikuchi
    • Organizer
      2nd GLowing Polymer Symposium in KANTO, 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核酸親和性薬物の目視スクリーニングを可能にするDNA修飾金ナノ粒子の界面設計2018

    • Author(s)
      秋山好嗣・齋川雄一・小久保有子・ナム ジェヨン・市橋理江・木村和徳・菊池明彦・宝田徹・前田瑞夫
    • Organizer
      第67回高分子学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 二重鎖DNA固定化金ナノ粒子を用いたDNA損傷剤の目視薬物探索2018

    • Author(s)
      木村和徳・秋山好嗣・宝田徹・前田瑞夫・菊池明彦
    • Organizer
      第67回高分子学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Colorimetric Screening of DNA-Functionalized Gold Nanoparticles with Drug-Nucleic Acid Interactions2018

    • Author(s)
      Yoshitsugu Akiyama
    • Organizer
      20th International Conference on Medicinal Chemistry and Rational Drugs
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] DNA密生型金ナノ粒子を用いたDNA損傷剤の目視アッセイ法の開発2018

    • Author(s)
      木村和徳、秋山好嗣、宝田徹、前田瑞夫、菊池明彦
    • Organizer
      第67回高分子討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] DNA切断活性を有する抗がん剤の目視探索への展開に向けたDNA二重鎖密生型金ナノ粒子の分散安定性評価2018

    • Author(s)
      秋山好嗣、木村和徳、菊池明彦、宝田徹、前田瑞夫
    • Organizer
      日本分析化学会第67回年会
    • Related Report
      2018 Research-status Report
  • [Presentation] DNA損傷剤の目視探索を目指したDNA密生型金ナノ粒子の分子設計2018

    • Author(s)
      木村和徳,秋山好嗣,宝田徹,前田瑞夫,菊池明彦
    • 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] A Simple Colorimetric Assay of Bleomycin-Mediated DNA Cleavage Based on Double-Stranded DNA-Modified Gold Nanoparticles2018

    • Author(s)
      Kazunori Kimura, Yoshitsugu Akiyama, Tohru Takarada, Mizuo Maeda, Akihiko Kikuchi
    • Organizer
      12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Colorimetric Detection of Anticancer Drug-Mediated DNA Cleavage Pathway Using Double-Stranded DNA-Functionalized Gold Nanoparticles2018

    • Author(s)
      Yoshitsugu Akiyama, Kazunori Kimura, Tohru Takarada, Mizuo Maeda, Akihiko Kikuchi
    • Organizer
      12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Colorimetric Assay of DNA Damaging Agents Utilizing Double-Stranded DNA-Functionalized Gold Nanoparticles2018

    • Author(s)
      Kazunori Kimura, Yoshitsugu Akiyama, Tohru Takarada, Mizuo Maeda,Akihiko Kikuchi
    • Organizer
      1st GLowing Polymer Symposium in KANTO
    • Related Report
      2018 Research-status Report
  • [Presentation] Colorimetric Assay of Bleomycin-Induced DNA Damage Utilizing Double-Stranded DNA-Functionalized Gold Nanoparticles2018

    • Author(s)
      Kazunori Kimura, Yoshitsugu Akiyama, Tohru Takarada, Mizuo Maeda, Akihiko Kikuchi
    • Organizer
      第28回日本MRS年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] DNA密生層を活用した界面設計とナノ診断・治療への応用2017

    • Author(s)
      秋山好嗣、木村和徳、川出茉実、菊池明彦
    • Organizer
      第3回東京理科大学総合研究院 再生医療とDDSの融合研究部門シンポジウム、第15回東京理科大学薬学部DDS研究センターシンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Remarks] 東京理科大学教員紹介

    • URL

      https://www.tus.ac.jp/fac_grad/p/achievement.php?3229

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] ポリ(カルバメート)-核酸医薬コンジュゲート、ポリ(カルバメート)核酸医薬コンジュゲートの凝集粒子、及び凝集粒子の製造方法2019

    • Inventor(s)
      秋山好嗣, 菊池明彦, 川出茉実, 木村和徳
    • Industrial Property Rights Holder
      秋山好嗣, 菊池明彦, 川出茉実, 木村和徳
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-164912
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] DNA損傷剤のスクリーニング方法及びDNA損傷剤のスクリーニング用キット2018

    • Inventor(s)
      秋山好嗣、菊池明彦、木村和徳
    • Industrial Property Rights Holder
      秋山好嗣、菊池明彦、木村和徳
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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