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New BNCT with development of new boron drugs targeting intracellular localization

Research Project

Project/Area Number 18K07324
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionOkayama University

Principal Investigator

Ichikawa Yasuaki  岡山大学, 中性子医療研究センター, 教授 (30126833)

Co-Investigator(Kenkyū-buntansha) 道上 宏之  岡山大学, 中性子医療研究センター, 准教授 (20572499)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsホウ素薬剤 / 中性子捕捉反応 / 薬物送達システム / アルファ崩壊 / BSH / 細胞内局在 / 細胞内導入 / ペプチドDDS / ホウ素中性子捕捉療法 / 悪性脳腫瘍 / 薬物送達システム(DDS) / ペプチド / 自己集合化 / 両親媒性 / 静電相互作用 / ホウ素中性子捕捉療法(BNCT) / グルコース / グルコース輸送体 / 中性子 / アミノ酸輸送体 / 癌治療 / がん治療 / BNCT / ホウ素製剤 / 創薬 / DDS
Outline of Final Research Achievements

The next-generation cancer treatment, boron neutron capture therapy (BNCT), destroys cells through a nuclear reaction between boron and neutrons. The neutron generator has been medically approved, and the success of BNCT in the future depends largely on the boron drug. It has been previously reported that secondary particles with a range of several micrometers generated by BNCT have different effects depending on the intracellular localization of boron drugs when inducing cytotoxicity into tumor cells. Furthermore, we have succeeded in introducing the first-generation boron drug BSH, which has been difficult to introduce into cells, into cells by forming a complex with DDS called A6K peptide. This will lead to the development of future boron drug development using new drugs.

Academic Significance and Societal Importance of the Research Achievements

BNCTにおいて、ホウ素薬剤の細胞内外の局在、及び細胞内の局在はその治療効果に大いに左右する。ホウ素薬剤は、甲状腺に対するヨウド剤(I)のように単体での取り込みは期待できない。そこで、ホウ素薬剤とどのような生理活性物質を組み合わせるのが重要である。今回我々は、細胞内導入能のない、細胞選択性のない第一世代ホウ素薬剤BSHに着目し、この二つの弱点を改善する薬剤開発に至った。その際、臨床使用されているペプチドDDSのA6Kペプチドに着目して、混合するだけで用事調整可能な薬剤を作製した。この薬剤による、経時的細胞内局在、脳腫瘍モデルマウスを用いた検証を行い、今後の薬剤の薬剤発展性に貢献した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (19 results) (of which Int'l Joint Research: 6 results,  Invited: 9 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Complementary Leucine Zippering System for Effective Intracellular Delivery of Proteins by Cell-Penetrating Peptides2021

    • Author(s)
      Mizuki Kitamatsu, Hiroki Yuasa, Takashi Ohtsuki, Hiroyuki Michiue
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 33 Pages: 116036-116041

    • DOI

      10.1016/j.bmc.2021.116036

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture therapy (BNCT)2021

    • Author(s)
      Michiue H, Kitamatsu M, Fukunaga A, Tsuboi N, Fujimura A, Matsushita H, Igawa K, Kasai T, Kondo N, Matsui H, Furuya S.
    • Journal Title

      J Control Release.

      Volume: 330 Pages: 788-796

    • DOI

      10.1016/j.jconrel.2020.11.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of Water Solubility of Mercaptoundecahydrododecaborate (BSH)-Peptides by Conjugating with Ethylene Glycol Linker and Interaction with Cyclodextrin2021

    • Author(s)
      Kitamatsu Mizuki、Nakamura-Tachibana Ayaka、Ishikawa Yoshimichi、Michiue Hiroyuki
    • Journal Title

      Processes

      Volume: 9 Issue: 1 Pages: 167-167

    • DOI

      10.3390/pr9010167

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A leucine zipper-based peptide hybrid delivers functional Nanog protein inside the cell nucleus.2019

    • Author(s)
      Yoshiyuki Hakata, Hiroyuki Michiue, Takashi Ohtsuki, Masaaki Miyazawa and Mizuki Kitamatsu
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 29 Issue: 7 Pages: 878-881

    • DOI

      10.1016/j.bmcl.2019.02.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxytocin inhibits corticosterone-induced apoptosis in primary hippocampal neurons.2018

    • Author(s)
      Hein Min Latt, Hiroaki Matsushita, Miku Morino, Yuuri Koga, Hiroyuki Michiue, Teiichi Nishiki, Kazuhito Tomizawa, Hideki Matsui
    • Journal Title

      Neuroscience

      Volume: - Pages: 383-389

    • DOI

      10.1016/j.neuroscience.2018.03.025

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Boron Neutron Capture Therapy Combined with Early Successive Bevacizumab Treatments for Recurrent Malignant Gliomas ? A Pilot Study2018

    • Author(s)
      SHIBA Hiroyuki、TAKEUCHI Koji、HIRAMATSU Ryo、FURUSE Motomasa、NONOGUCHI Naosuke、KAWABATA Shinji、KUROIWA Toshihiko、KONDO Natsuko、SAKURAI Yoshinori、SUZUKI Minoru、ONO Koji、OUE Shiro、ISHIKAWA Eiichi、MICHIUE Hiroyuki、MIYATAKE Shin-Ichi
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 58 Issue: 12 Pages: 487-494

    • DOI

      10.2176/nmc.oa.2018-0111

    • NAID

      130007531206

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] グルコース輸送体標的ホウ素薬剤による悪性脳腫瘍BNCTの新しい戦略2020

    • Author(s)
      道上宏之
    • Organizer
      第79回日本脳神経外科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] グルコース輸送体を標的とした新規ホウ素製剤開発へ向けて2020

    • Author(s)
      道上宏之
    • Organizer
      令和2年度京都大学複合原子力科学研究所専門研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 「ホウ素薬剤開発の現状 ~基礎研究より橋渡し研究へ向けて~2020

    • Author(s)
      道上宏之
    • Organizer
      令和2年度 第1回量子医療研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 両親媒性ペプチドを用いたホウ素ペプチド創薬2020

    • Author(s)
      道上宏之
    • Organizer
      「ナノ・バイオ融合によるエネルギー集積・高度利用研究拠点形成」   シンポジウム 「ペプチドの新たな未来へ向けて」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The role of calcineurin in controlling cell function in hair generation2020

    • Author(s)
      Hiroyuki Michiue
    • Organizer
      National Symposium and Workshop in Anti-Aging Medicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Translational research in hair generation from lab to life2020

    • Author(s)
      Hiroyuki Michiue
    • Organizer
      National Symposium and Workshop in Anti-Aging Medicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] New drug discovery with drug re-positioning system toward GBM treatment2019

    • Author(s)
      Hiroyuki Michiue, Nobushige Tsuboi, Keiichiro Hayashi, Hideki Matsui, Kazuhiko Kurozumi
    • Organizer
      2019 Society of Neuro-Oncology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] New peptide Drug Delivery System with BSH toward future BNCT clinical application2019

    • Author(s)
      Hiroyuki Michiue, Asami Fukunaga, Mizuki Kitamatsu, Natsuko Kondo, Yoshinori Sakurai, Atsushi Fujimura, Kazuyo Igawa, Hideki Matsui, Shuichi Furuya
    • Organizer
      10th Young Reserchers BNCT Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ペプチドDDSを用いた新規ホウ素 薬剤製剤化への取り組み2019

    • Author(s)
      道上宏之
    • Organizer
      第3回NTRCシンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] The cell biological evaluation with Nagoya University BNCT system2019

    • Author(s)
      道上宏之, 井川和代, 古矢修一, 市川康明, 吉橋幸子, 瓜谷章, 渡辺賢一, 鬼柳善明, 土田一輝
    • Organizer
      第16回日本中性子捕捉療法学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ホウ素中性子捕捉療法(BNCT)のメラノーマ治療における位置づけ~BNCTの基礎より最新の研究まで~2018

    • Author(s)
      道上宏之
    • Organizer
      第6回岡山メラノーマ治療研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 再発メラノーマに対するBNCTを含めた新規集学的治療の取り組み2018

    • Author(s)
      道上宏之
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ペプチドDDSを用いた新規ホウ素薬剤の構築2018

    • Author(s)
      道上宏之 福永麻美 北松瑞生  近藤夏子  櫻井良憲  藤村篤史  井川和代  松井秀樹  古矢修一
    • Organizer
      第15回日本中性子捕捉療法学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] New multidisciplinary treatment with Boron Neutron Capture Therapy (BNCT) against melanoma2018

    • Author(s)
      道上宏之
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] New self-assembling peptide Drug Delivery System with BSH toward clinical application2018

    • Author(s)
      道上宏之
    • Organizer
      18th International Congress on Neutron Capture Therapy (ICNCT-18)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] New A6k boron drug delivery system for clinical application of Boron Neutron Capture Therapy (BNCT)2018

    • Author(s)
      道上宏之
    • Organizer
      2018 Annual Meeting and Education Day of the Society for Neuro-Oncology.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] BNCTを用いた新規岡山大学メラノーマ集学的治療へ向けた取り組み2018

    • Author(s)
      道上宏之
    • Organizer
      第2回中性子医療研究センターシンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] BNCT治療の現実とこれから2018

    • Author(s)
      道上宏之
    • Organizer
      第2回中性子医療研究センターシンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 脳腫瘍幹細胞由来の腫瘍血管を標的とした新規抗血管新生療法の開発2018

    • Author(s)
      道上宏之
    • Organizer
      第36回日本脳腫瘍学会学術集会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] グルコース結合ホウ素薬剤2020

    • Inventor(s)
      道上宏之
    • Industrial Property Rights Holder
      道上宏之
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] グルコースホウ素薬剤2020

    • Inventor(s)
      道上宏之 高口豊
    • Industrial Property Rights Holder
      道上宏之 高口豊
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-051323
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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