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Development of Boron Delivery System for Neutron Capture Therapy as a Minimally Invasive Cancer Therapy

Research Project

Project/Area Number 23390013
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionTokyo Institute of Technology (2012-2013)
Gakushuin University (2011)

Principal Investigator

NAKAMURA Hiroyuki  東京工業大学, 資源化学研究所, 教授 (30274434)

Co-Investigator(Kenkyū-buntansha) SATO Shinichi  東京工業大学, 資源化学研究所, 助教 (20633134)
Co-Investigator(Renkei-kenkyūsha) SUZUKI Minoru  京都大学, 原子炉実験所, 教授 (00319724)
BAN Hyun Seung  学習院大学, 理学部, 助教 (60433710)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords中性子捕捉療法 / リポソーム / ドラッグデリバリーシステム / ホウ素ナノカプセル / ドラッグデリバリー / ホウ素 / がん治療 / 低侵襲 / 有機化学 / 癌
Outline of Final Research Achievements

Boron neutron capture therapy (BNCT) is based on the capture reaction of thermal neutrons and nonradioactive 10B, which produces an α-particle and a lithium-7 nuclei ion with approximately 2.4 MeV. We developed the liposomes with high boron contents as efficient boron delivery vehicles for BNCT. We optimized DSBL contents in the liposome preparation and found that 10% DSBL liposome is stable in blood circulation. Furthermore, we succeeded in encapsulation of BSH into the vacant inner of the 10% DSBL liposomes, producing the liposomes with high boron contents. We examined boron biodistribution in the tumor-bearing mice by injection of BSH-encapsulating DSBL liposomes via the tail vein. High boron accumulation was observed in the tumor tissue 36 h after injection of the liposomes. Significant tumor growth suppression was observed in the boron-loaded mice after neutron irradiation.

Report

(4 results)
  • 2014 Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (49 results)

All 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Acknowledgement Compliant: 4 results) Presentation (33 results) (of which Invited: 10 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Synthesis of protoporphyrin lipids and biological evaluation of micelles and liposomes2014

    • Author(s)
      S. Tachikawa, M. E. El-Zaria, R. Inomata, S. Sato, H. Nakamura
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 22 Issue: 17 Pages: 4745-4751

    • DOI

      10.1016/j.bmc.2014.07.003

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel photodynamic therapy for drug resistant prostate cancer cells using porphyrus Envelope as a novel photosensitizer2014

    • Author(s)
      M. Yamauchi, N. Honda, H. Hazama, S. Tachikawa, H. Nakamura, Y. Kaneda, K. Awazu
    • Journal Title

      Photodiagnosis and Photodynamic Therapy

      Volume: 11 Issue: 1 Pages: 48-54

    • DOI

      10.1016/j.pdpdt.2013.10.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Towards new boron carriers for boron neutron capture therapy: metallacarboranes and their cholesterol conjugates2013

    • Author(s)
      M. Bialek-Pietras, A. B. Olejniczak, S. Tachikawa, H. Nakamura, Z. J. Lesnikowski
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 21 Issue: 5 Pages: 1136-1142

    • DOI

      10.1016/j.bmc.2012.12.039

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Boron lipid-based liposomal boron delivery system for neutron capture therapy: recent development and future perspective2013

    • Author(s)
      H. Nkamura
    • Journal Title

      Future Medicinal Chemistry

      Volume: 5 Issue: 6 Pages: 715-730

    • DOI

      10.4155/fmc.13.48

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of High Boron Content Liposomes and Their Promising Antitumor Effect for Neutron Capture Therapy of Cancers2013

    • Author(s)
      Hayato Koganei, Manabu Ueno, Shoji Tachikawa, Lisa Tasaki, Hyun Seung Ban, Minoru Suzuki, Kouichi Shiraishi, Kumi Kawano, Masayuki Yokoyama, Yoshie Maitani, Koji Ono, and Hiroyuki Nakamura
    • Journal Title

      Bioconjugate Chemistry

      Volume: 24 Issue: 1 Pages: 124-132

    • DOI

      10.1021/bc300527n

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design and synthesis of fluorescence-labeled close-dodecaborate lipid: its liposome formation and in vivo imaging targeting of tumors for boron neutron capture therapy2012

    • Author(s)
      Nakamura H, Ueda N, Bam HS, Ueno M, Tachikawa S
    • Journal Title

      Org. Biomol. Chem.

      Volume: 10 Issue: 7 Pages: 1374-80

    • DOI

      10.1039/c1ob06500a

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and biological evaluation of boronic acid containing phenstatin analogues2012

    • Author(s)
      H. Nakamura, H. Kuroda, H. Minegishi,
    • Journal Title

      ARKIVOC

      Volume: 7 Issue: 7 Pages: 79-87

    • DOI

      10.3998/ark.5550190.0013.705

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro investigation of efficient Photodynamic Therapy using non-viral vector; Hemagglutinating virus of Japan envelope2012

    • Author(s)
      N. Fujimoto, M. Sakai, K. Ishii, H. Nakamura, Y. Kaneda, K. Awazu
    • Journal Title

      J. Biomed. Opt.

      Volume: 17 Issue: 7 Pages: 78002-78002

    • DOI

      10.1117/1.jbo.17.7.078002

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biological evaluation of dopamine analogues containing phenylboronic acid group as new boron carriers2011

    • Author(s)
      Y. Ito, T. Mizuno, K. Yoshino, H.S. Ban, H. Nakamura, J. Hiratsuka, A. Ishikawa, H. Ohki
    • Journal Title

      Appl. Radiat. Isotope

      Volume: 69 Issue: 12 Pages: 1771-1773

    • DOI

      10.1016/j.apradiso.2011.04.004

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-inducible factor inhibitors : A survey of recent patented compounds(2004-2010)2011

    • Author(s)
      Hyun Seung Ban, Yoshikazu Uto, Hiroyuki Nakamura
    • Journal Title

      Expert Opinion on Therapeutic Patents

      Volume: 21(2) Issue: 2 Pages: 131-146

    • DOI

      10.1517/13543776.2011.547477

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 今後、治療の多様化に適応できるホウ素薬剤の開発を2011

    • Author(s)
      中村浩之
    • Journal Title

      エネルギーレビュー

      Volume: 31 Pages: 17-18

    • Related Report
      2011 Annual Research Report
  • [Presentation] がん光線力学的療法のためのPpIX脂質導入ナノキャリアの開発とその効果2014

    • Author(s)
      立川将士,佐藤伸一,山内将哉,間久直, 粟津邦男,金田安史, 中村浩之
    • Organizer
      日本薬学会第134回年会
    • Place of Presentation
      熊本大学(熊本)
    • Year and Date
      2014-03-27 – 2014-03-30
    • Related Report
      2013 Annual Research Report
  • [Presentation] ホウ素創薬の最前線2013

    • Author(s)
      中村浩之
    • Organizer
      CBI学会2013年大会
    • Place of Presentation
      船堀タワーホール(東京)
    • Year and Date
      2013-10-31
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Development of high boron content molecules and their liposome encapsulation for neutron capture therapy2013

    • Author(s)
      H. Koganei, S. Tachikawa, M. Suzuki, K. Ono, and H. Nakamura
    • Organizer
      7th Young Researchers In Boron Neutron Capture Therapy Meeting
    • Place of Presentation
      タラゴナ(スペイン)
    • Year and Date
      2013-09-23 – 2013-09-26
    • Related Report
      2013 Annual Research Report
  • [Presentation] 生体高分子への簡便なホウ素導入法の開発とDDSへの展開2013

    • Author(s)
      加納 大輔、立川 将士、佐藤 伸一、中村 浩之
    • Organizer
      第10回日本中性子捕捉療法学会
    • Place of Presentation
      岡山大学(岡山)
    • Year and Date
      2013-09-07 – 2013-09-08
    • Related Report
      2013 Annual Research Report
  • [Presentation] がんを治す薬―人々の夢実現に向けて―2013

    • Author(s)
      中村浩之
    • Organizer
      読売サイエンスフォーラム
    • Place of Presentation
      学習院大学(東京都豊島区)
    • Year and Date
      2013-07-27
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] がん光線力学的治療のためのポルフィリン脂質の開発とナノキャリアーへの応用2013

    • Author(s)
      立川将士、佐藤伸一、中村浩之
    • Organizer
      第23回日本光線力学学会学術講演会
    • Place of Presentation
      旭川医科大学(旭川)
    • Year and Date
      2013-06-07 – 2013-06-08
    • Related Report
      2013 Annual Research Report
  • [Presentation] Evaluation of protoporphyrin IX combined with lipid chains as a novel photosensitizer2013

    • Author(s)
      Masaya Yamauchi, Norihiro Honda, Hisanao Hazama, Shoji Tachikawa, Hiroyuki Nakamura, Yasufumi Kaneda, and Kunio Awazu
    • Organizer
      The 14th World Congress of the International Photodynamic Association
    • Place of Presentation
      釜山(韓国)
    • Year and Date
      2013-05-28 – 2013-06-01
    • Related Report
      2013 Annual Research Report
  • [Presentation] ピレンを発光団としたけい光リン脂質におけるけい光異方性のピコ秒時間分解測定‐DMPCリポソーム脂質二重膜中の粘土の回転緩和時間からの見積もり2013

    • Author(s)
      野嶋優妃、加納大輔、中村浩之、岩田耕一
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      滋賀
    • Related Report
      2012 Annual Research Report
  • [Presentation] ホウ素高集積化リポソームによる中性子捕捉治療抗腫瘍効果の改善2013

    • Author(s)
      中村浩之
    • Organizer
      第133回日本薬学会年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ピレン基を有するリン脂質の合成とけい光異方性のピコ秒時間分解測定によるリポソーム脂質二重膜中の粘度の見積もり2013

    • Author(s)
      加納大輔、野嶋優妃、岩田耕一
    • Organizer
      第133回日本薬学会年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dodecaborate Lipid Liposomes as New Vehicles for Boron Delivery System of Neutron Capture Therapy2012

    • Author(s)
      H. Nakamura
    • Organizer
      The 13th Boron In The Americas Conference(USA)
    • Place of Presentation
      アメリカ合衆国
    • Related Report
      2012 Annual Research Report
  • [Presentation] ホウ素脂質リポソームの開発と中性子捕捉治療効果2012

    • Author(s)
      中村 浩之、三好達郎、立川将士、小金井逸人、鈴木実、小野公二
    • Organizer
      日本DDS学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cholesterol-boron cluster conjugates:Synthesis via dioxane ring opening of the oxonium derivative of the boron cluster and preliminary physicochemical and biological evaluation2012

    • Author(s)
      Magdalena Bialek-Pietras, Agnieszka B. Olejniczak, S. Tachikawa, H. Nakamura, Z. J. Lesnikowski
    • Organizer
      4th Congress of the European Association for Chemical and Molecular Sciences
    • Place of Presentation
      チェコ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Pretreatment with buthionine sulfoximine enhanced uptake and retention of BSH for BNCT2012

    • Author(s)
      F. Yoshida, K. Nakei, T. Yamamoto, M. Shirakawa, H. Nakamura、 Alexander Zaboronok, Akira Matsumura,
    • Organizer
      15th International congress on Neutron Capture Therapy
    • Place of Presentation
      筑波
    • Related Report
      2012 Annual Research Report
  • [Presentation] closo-Dodecaborate-conjugated cholesterols:Synthesis and click imaging of their liposomesin cells2012

    • Author(s)
      H. Nakamura, T. Miyoshi, S. Tachikawa, H. Koganei, S. Kojima, M. Suzuki, K. Ono
    • Organizer
      15th International congress on Neutron Capture Therapy
    • Place of Presentation
      筑波
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Development of liposomal boron agents for neutron capture therapy2012

    • Author(s)
      S. Tachikawa, T. Miyoshi, H. Koganei, D. Kanoh, H. Ban, M. Suzuki, M. Kirrihara, K. Ono, H. Nakamura
    • Organizer
      15th International congress on Neutron Capture Therapy
    • Place of Presentation
      筑波
    • Related Report
      2012 Annual Research Report
  • [Presentation] ホウ素リポソームの高集積化を目指して2012

    • Author(s)
      中村浩之
    • Organizer
      平成23年度京都大学原子炉実験所専門研究会
    • Place of Presentation
      大阪
    • Related Report
      2011 Annual Research Report
  • [Presentation] Antitumor Activity of Boron Lipid Liposomes with Neutron Irradiation2012

    • Author(s)
      Hayato Koganei, Shoji Tachikawa, Minoru Suzuki, Koji Ono, Hiroyuki Nakamura
    • Organizer
      SIMS2012
    • Place of Presentation
      つくば
    • Related Report
      2011 Annual Research Report
  • [Presentation] ホウ素脂質リポソームの 中性子照射における抗腫瘍効果2012

    • Author(s)
      小金井逸人、立川将士、三好達郎, 鈴木実、小野公二, 中村浩之
    • Organizer
      第132回日本薬学会年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Annual Research Report
  • [Presentation] Possibility of Liposomal Boron Delivery System in BNCT2011

    • Author(s)
      H. Nakamura
    • Organizer
      Trilaterla Meeting on BNCT
    • Place of Presentation
      大阪
    • Related Report
      2011 Annual Research Report
  • [Presentation] 中性子でがんを治す‐がん細胞内部で放射線を発生させる次世代治療法とは?‐2011

    • Author(s)
      中村浩之
    • Organizer
      第27回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] がん中性子捕捉療法のための高集積ホウ素ナノデバイスの開発2011

    • Author(s)
      立川 将士、猪俣 竜、三好 達郎、潘 鉉承、李 千萬、柳衛 宏宣、鈴木 実、小田 雄介、丸山 一雄、中村 浩之
    • Organizer
      第27回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] がんの低酸素環境応答と創薬ターゲット2011

    • Author(s)
      中村 浩之
    • Organizer
      有機合成化学協会ミニシンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] 高集積化ホウ素ナノデバイスの開発2011

    • Author(s)
      立川将士、三好達郎、小金井逸人、潘鉉承、鈴木実、小野公二、中村浩之
    • Organizer
      第8回日本中性子捕捉療法学会学術集会
    • Place of Presentation
      徳島
    • Related Report
      2011 Annual Research Report
  • [Presentation] Development of Liposomal Boron Agents for Neutron Capture Therapy2011

    • Author(s)
      Shoji Tachikawa, Hyun Seung, Ban, Hiroyuki Nakamura
    • Organizer
      AIMECS11
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] Development of Liposomal Boron Delivery System for Neutron Capture Therapy2011

    • Author(s)
      Hiroyuki Nakamura
    • Organizer
      6th Young BNCT Meeting
    • Place of Presentation
      台北
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Development of Liposomal Boron Agents for Neutron Capture Therapy2011

    • Author(s)
      Shoji Tachikawa, Tatsuro Miyoshi, Hayato Koganei, Daisuke Kanoh, Hyun Seung, Ban, Hiroyuki Nakamura
    • Organizer
      6th Young BNCT Meeting
    • Place of Presentation
      台北
    • Related Report
      2011 Annual Research Report
  • [Presentation] ホウ素でがんに挑む

    • Author(s)
      中村 浩之
    • Organizer
      第69回学習院大学理学部技術交流会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Boron-Based Drug Design: From Chemical Biology to Neutron Capture Therapy

    • Author(s)
      H. Nakamura
    • Organizer
      Paris Tech Seminar
    • Place of Presentation
      フランス
    • Related Report
      2012 Annual Research Report
  • [Presentation] 高ホウ素化リポソームの開発と中性子照射による抗腫瘍効果

    • Author(s)
      小金井 逸人、上野 学、立川 将士、鈴木 実、小野 公二、中村 浩之
    • Organizer
      第21回DDSカンファランス
    • Place of Presentation
      静岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Boron-Based Drug Design: From Chemical Biology to Neutron Capture Therapy

    • Author(s)
      H. Nakamura
    • Organizer
      Poland Academy of Science, Seminar
    • Place of Presentation
      ポーランド
    • Related Report
      2012 Annual Research Report
  • [Presentation] closo-Dodecaborate-conjugated cholesterols: Synthesis and click imaging of their liposomes in cells

    • Author(s)
      H. Nakamura
    • Organizer
      Trilaterla Meeting of BNCT in Taipei
    • Place of Presentation
      台北
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 中性子でがんを治す次世代の放射線療法

    • Author(s)
      中村浩之
    • Organizer
      学際生命科学東京コンソーシアム 第7回市民講演会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] 医学物理の理工学(下巻)2013

    • Author(s)
      上坂充、中川恵一、金井達明、西尾禎治
    • Total Pages
      274
    • Publisher
      養賢堂
    • Related Report
      2013 Annual Research Report
  • [Book] Springer2012

    • Author(s)
      W. A. G. Sauerwein, A. Wittig, R. Moss, Y. Nakagawa
    • Total Pages
      553
    • Publisher
      Neutron Capture Therapy -Principles and Applications
    • Related Report
      2012 Annual Research Report
  • [Book] Boron Science: New Technologies and Applications2011

    • Author(s)
      N. S. Hosman
    • Total Pages
      850
    • Publisher
      CRC Press
    • Related Report
      2011 Annual Research Report
  • [Remarks] 東京工業大学資源化学研究所合成化学部門中村研究室

    • URL

      http://www.syn.res.titech.ac.jp

    • Related Report
      2012 Annual Research Report
  • [Remarks] 学習院大学理学部化学科中村研究室

    • URL

      http://www-cc.gakushuin.ac.jp/~20021059/index.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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