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Development of carrier molecule targeted GLUT

Research Project

Project/Area Number 20K05755
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionOkayama University (2022)
Tokyo University of Science (2020-2021)

Principal Investigator

Tanaka Tomohiro  岡山大学, 医歯薬学域, 准教授 (20711667)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsホウ素中性子線捕捉療法 / BSH / キャリア分子 / カチオン性ポリマー / ホウ素クラスター / ホウ素中性子線補足療法 / グルコーストランスポータ / 亜鉛錯体 / メディシナルケミストリー
Outline of Research at the Start

近年、がん治療の新たな選択肢の一つとしてホウ素中性子線捕捉療法(BNCT: Boron Neutron Capture Therapy)が注目されている。BNCTは10B化合物に中性子線を当てることによりα線を発生させることでその周囲の細胞を死滅させるものであるが、その実用化に向けての最も大きい課題は線源となりうる10B化合物を如何にしてがん細胞に集めるかということである。そこで、本研究課題ではがん細胞が独自の糖代謝系を有している事(ワールブルグ効果)に注目し、グルコーストランスポーターによってがん細胞に輸送され、配位結合によってBSHを担持可能なキャリア分子の創製研究を提案する。

Outline of Final Research Achievements

In this research, we developed a technology to deliver BSH, which is used as a BNCT drug, into cells. The original plan was to develop carrier molecules that induce GLUT-mediated uptake, but we found that nanoparticles could be formed by mixing BSH with cationic polymers. Therefore, we decided to focus on these nanoparticles. When the cytotoxicity and cell membrane permeability of this nanoparticle were evaluated, it was revealed that the membrane permeability was significantly improved compared to BSH alone.

Academic Significance and Societal Importance of the Research Achievements

BSHは構造中に複数のホウ素原子を有している事からBNCT用薬剤として有用であるにもかかわらず、その細胞膜透過性の低さからあまり使用されていない。本研究成果によってカチオン性ポリマーを混合するだけで、BSHの欠点である膜透過性を改善できたという点は今後のBNCT研究に大きく貢献するものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (30 results)

All 2023 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (23 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Effect of N-Benzyl Group in Indole Scaffold of Thiosemicarbazones on the Biological Activity of Their Pd(II) Complexes: DFT, Biomolecular Interaction, in Silico Docking, ADME and Cytotoxicity Studies2022

    • Author(s)
      Nithya Balakrishnan, Jebiti Haribabu, Rahime Eshaghimalekshah, Srividya Swaminathan, Chandrasekar Balachandran, Nattamai S.P. Bhuvanesh, Shin Aoki, Ramasamy Karvembu,
    • Journal Title

      Inorganica Chimica Acta

      Volume: 534 Issue: 5

    • DOI

      10.1002/ejic.202100949

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential Anti-COVID-19 Agents, Cepharanthine and Nelfinavir, and Their Usage for Combination Treatment2021

    • Author(s)
      H. Ohashi, K. Watashi, W. Saso, K. Shionoya, et al.
    • Journal Title

      iScience

      Volume: 24 Issue: 4 Pages: 335-337

    • DOI

      10.1016/j.isci.2021.102367

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isohamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome2021

    • Author(s)
      Yuichi Nishiyama, Akinori Morita, Shogo Tatsuta, Misaki Kanamaru, Masahiro Sakaue, Kenta Ueda, Manami Shono, Rie Fujita, Bing Wang, Yoshio Hosoi, Shin Aoki and Takeshi Sugai
    • Journal Title

      Genes

      Volume: 12 Issue: 12 Pages: 8523-8544

    • DOI

      10.1021/acs.jmedchem.1c00445

    • Related Report
      2021 Research-status Report
  • [Journal Article] Development of Metallosupramolecular Phosphatases Based on Combinatorial Self-Assembly of Metal Complexes and Organic Building Blocks for Catalytic Hydrolysis of Phosphate Monoesters2021

    • Author(s)
      S. Aoki, A. B. Rahman, Y. Hisamatsu, Y. Miyazawa, M. Zulkefeli, Y. Saga, and Tomohiro Tanaka
    • Journal Title

      Results in Chemistry (a joint special issue with Inorganica Chimica Acta)

      Volume: 3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential Anti-COVID-19 Agents, Cepharanthine and Nelfinavir, and Their Usage for Combination Treatment2021

    • Author(s)
      H. Ohashi, K. Watashi, T. Tanaka, S. Aoki 他26名
    • Journal Title

      iScience

      Volume: 24

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy.2020

    • Author(s)
      N. Kuwabara, R. Imae, H. Manya, T. Tanaka, M. Mizuno, H. Tsumoto, M. Kanagawa, K. Kobayashi, T. Toda, T. Senda, T. Endo & R. Kato
    • Journal Title

      NAT COMMUN

      Volume: 11

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ホウ素中性子線捕捉療法のための BSH/CPナノ粒子の開発2023

    • Author(s)
      田中智博、上田大貴、鈴木実、櫻井良憲、上田真史、青木伸
    • Organizer
      日本薬学会第143回年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of Nanoparticle Composed of BSH and Cationic Polymer for Boron Neutron Capture Therapy (BNCT)2022

    • Author(s)
      Tomohiro Tanaka
    • Organizer
      icpac kota kinabalu 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗マラリア薬アモジアキンをリード化合物とした抗SARS-CoV-2治療薬の創製2022

    • Author(s)
      田中智博、横井健汰、佐藤秀哉、森田都望恵、岡本実佳、外山政明、馬場昌範、青木伸
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Research-status Report
  • [Presentation] ホウ素中性子捕捉療法のための新規ポリアミン誘導体の開発2021

    • Author(s)
      上田大貴 、田中智博 、鈴木実 、青木伸
    • Organizer
      第30回金属の関与する生体関連反応シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 情報科学及び機械工学と連携した抗SARS-CoV-2治療薬の設計及び合成2021

    • Author(s)
      内山 遥、田中 智博、大橋 啓史、塩野谷 果歩、渡士 幸一、倉持 幸司、秋本 康平、竹村 裕、岡本 実佳、外山 政明、馬場 昌範、青木 伸
    • Organizer
      第65回日本薬学会関東支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 選択的セロトニン再取り込み阻害薬SSRIの抗炎症効果の解明2021

    • Author(s)
      竹中洋平、北畠和己、田中智博、青木伸、月本光俊
    • Organizer
      第65回日本薬学会関東支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] cis型アゾベンゼンを含むキラル大環状化合物の合成と異性化反応の検討2021

    • Author(s)
      芝内涼太、田中智博、青木伸
    • Organizer
      第65回日本薬学会関東支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of Boron-containing Macrocyclic Polyamines and Their Zn(Ⅱ) Complexes for Boron Neutron Capture Therapy2021

    • Author(s)
      上田大貴 、田中智博 、鈴木実 、青木伸
    • Organizer
      錯体化学会第71回討論会
    • Related Report
      2021 Research-status Report
  • [Presentation] Design and Synthesis of Poly(2,2’-bipyridyl) Ligands Directed toward Chelation Therapy of Cancer2021

    • Author(s)
      Masumi Hirose, Zhu Jun Jie, Chandrasekar Balacahndran, Tomohiro Tanaka, Yosuke Hisamatsu, Yasuyuki Yamada, Shin Aoki
    • Organizer
      International Research Network Initiative (IRNI) and 8th International Postgraduate Conference on Pharmaceutical Sciences 2021 (iPoPS2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Mefloquine Has a Potent Antiviral Activity against Severe Acute Respiratory Syndrome Related Coronavirus 22021

    • Author(s)
      Kaho Shionoya, Masako Yamasaki, Shoya Iwanami, Yusuke Ito, Shuetsu Fukushi, Hirofumi Ohashi, Wakana Saso, Tomohiro Tanaka, Shin Aoki, Kouji Kuramochi, Shingo Iwami, Yoshimasa Takahashi, Tadaki Suzuki, Masamichi Muramatsu, Makoto Takeda, Takaji Wakita and Koichi Watashi
    • Organizer
      第68回日本ウイルス学会学術学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of Nanoparticle Composed of BSH and Cationic Polymer for Boron Neutron Capture Therapy (BNCT)2021

    • Author(s)
      Tomohiro Tanaka, Hiroki Ueda, Shin Aoki, Minoru Suzuki, Yoshinori Sakurai
    • Organizer
      13th AFMC International Medicinal Chemistry Symposium (AIMECS 2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Design, Synthesis, and BNCT (Boron Neutron Capture Therapy) Activity of Boron-Containing Macrocyclic Polyamines2021

    • Author(s)
      Hiroki Ueda, Minoru Suzuki, Tomohiro Tanaka, Shin Aoki
    • Organizer
      13th AFMC International Medicinal Chemistry Symposium (AIMECS 2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Design, Synthesis, and Antiviral Activity of Anti-SARS-CoV-2 Agents in Interdisciplinary Research2021

    • Author(s)
      Haruka Uchiyama, Mayuka Nii, Tomohiro Tanaka, Kohei Akimoto, Hiroshi Takemura, Kaho Shionoya, Hirofumi Ohashi, Koichi Watashi, and Shin Aoki
    • Organizer
      2020/2021 International Chemical Congress of Pacific Basin Societies (PACICHEM2020/2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Design, Synthesis, and Anti-SARS-CoV-2 Activity of Amodiaquine Analogs2021

    • Author(s)
      Tomoe Morita, Tomohiro Tanaka, Kenta Yokoi, Hidetoshi Sato, Mika Okamoto, Masaaki Toyama, Masanori Baba, and Shin Aoki
    • Organizer
      2020/2021 International Chemical Congress of Pacific Basin Societies (PACICHEM2020/2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of Light-driven Molecular Machines that Perform Unidirectional Motion2021

    • Author(s)
      Ryota Shibauchi, Ong Yong Liang, Mohd Zulkefeli, Tomohiro Tanaka, Shin Aoki
    • Organizer
      2020/2021 International Chemical Congress of Pacific Basin Societies (PACICHEM2020/2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of Nanoparticle Composed of BSH and Cationic Polymer for Boron Neutron Capture Therapy (BNCT)2021

    • Author(s)
      Tomohiro Tanaka, Hiroki Ueda, Shin Aoki, Minoru Suzuki, Yoshinori Sakurai
    • Organizer
      2020/2021 International Chemical Congress of Pacific Basin Societies (PACICHEM2020/2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of Boron-containing Macrocyclic Polyamine Derivatives for Boron Neutron Capture Therapy2021

    • Author(s)
      Hiroki Ueda, Taiki Itoh, Kosuke Mizuno, Tomohiro Tanaka, Minoru Suzuki, Yoshinori Sakurai, and Shin Aoki
    • Organizer
      2020/2021 International Chemical Congress of Pacific Basin Societies (PACICHEM2020/2021)
    • Related Report
      2021 Research-status Report
  • [Presentation] ホウ素中性子捕捉療法のための新規ポリアミン誘導体の開発2021

    • Author(s)
      〇上田大貴 1、田中智博 1、鈴木実 2、櫻井良憲 2、青木伸 1,3(1東京理大薬、2京大複合研、 3東京理大総合研究院)
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] カチオン性ポリマーを用いたホウ素中性子線捕捉療法のためのBSH含有ナノ粒子の開発2021

    • Author(s)
      〇田中智博 1、上田大貴 1、鈴木実 2、櫻井良憲 2、青木伸 1,3(1東京理大薬、2京大複合研、 3東京理大総合研究院)
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] ホウ素中性子捕捉療法を指向したBSH含有ナノ粒子の開発2020

    • Author(s)
      〇田中智博 1、上田大貴 1、鈴木実 2、櫻井良憲 2、青木伸 1,3(1東京理大薬、2京大複合研、 3東京理大総合研究院)
    • Organizer
      京都大学複合原子力科学研究所 第55回学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] ホウ素中性子捕捉療法のためのポリアミン誘導体の創製2020

    • Author(s)
      〇上田大貴 1、田中智博 1、鈴木実 2、櫻井良憲 2、青木伸 1,3(1東京理大薬、2京大複合研、 3東京理大総合研究院)
    • Organizer
      京都大学複合原子力科学研究所 第55回学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] ホウ素中性子線捕捉療法のための BSH 含有ナノ粒子の創製2020

    • Author(s)
      〇田中智博 1、上田大貴 1、鈴木実 2、櫻井良憲 2、青木伸 1,3(1東京理大薬、2京大複合研、 3東京理大総合研究院)
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Research-status Report
  • [Presentation] BNCT 用ポリアミン誘導体の設計・合成および生物学的評価2020

    • Author(s)
      〇上田大貴 1、田中智博 1、鈴木実 2、櫻井良憲 2、青木伸 1,3(1東京理大薬、2京大複合研、 3東京理大総合研究院)
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 抗SARS-CoV-2薬2021

    • Inventor(s)
      馬場昌範、岡本美佳、外山政明、青木伸、田中智博、横井健汰
    • Industrial Property Rights Holder
      馬場昌範、岡本美佳、外山政明、青木伸、田中智博、横井健汰
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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