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Development and Validation of Safe and Efficient Multi-functional Boron Nanoformulation for Next-generation BNCT

Research Project

Project/Area Number 18K07256
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 InstitutionUniversity of Tsukuba

Principal Investigator

Matsumoto Yoshitaka  筑波大学, 医学医療系, 助教 (70510395)

Co-Investigator(Kenkyū-buntansha) 長崎 幸夫  筑波大学, 数理物質系, 教授 (90198309)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsホウ素中性子捕捉療法(BNCT) / ホウ素製剤 / フェニルボロン酸(PBA) / シアル酸 / ナノ粒子 / DDS / 超分子構造 / BNCT / フェニルボロン酸 / ホウ素中性子捕捉療法 / 放射線治療 / ホウ素化合物 / EPR効果 / PBA / 粒子線治療
Outline of Final Research Achievements

BPA-f complexes used in boron neutron capture therapy are preferentially taken up in tumors by amino acid transporters, but their retention in tumors is limited by anti-port mechanisms. We employed phenylboronic acid (PBA)-modified polymeric nanoparticles (PBA-NPs) as a sialic acid-targeted boron formulation. the PBA can exhibit dual functionalities, i.e.,PBA exhibiting a neutron capture capacity and hypersialyated cancer cell targeting effect. Our developed Nano possesses a supramolecular structure composed of a core and shell comprised of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) segments, respectively. The PBA moiety is installed at the PEG end, providing an unusually strong targeting effect, supposedly via multivalent binding onto the cancer cell membrane. As in BNCT, we verified the feasibility of PBA-NP against a B16 melanoma-bearing mouse model. The PBA-NP achieved a potent antitumor effect even at a 100-fold lower dose than BPA-f.

Academic Significance and Societal Importance of the Research Achievements

現在臨床のBNCTで用いるホウ素製剤であるステボロニン(BPAとソルビトールとの複合体)は、集積する癌種が制限されること、アンチポート機構による腫瘍からのクリアランスが早いことなどが課題として挙げられている。今回開発および効果を検証したPBA-NPは、ステボロニンとは異なる癌細胞選択的機序機能を有しており、これまではBNCT適応外とされた癌種や患者に対して、BNCTを提供できる可能性を有する。また、血中および腫瘍内への滞留性が優れることから、ステボロニンのような照射前から照射中に渡る連続的な薬剤投与は不要となり、薬剤投与の簡便化と安全性の向上に資すると考える。

Report

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

    (41 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 2 results) Presentation (24 results) (of which Int'l Joint Research: 11 results,  Invited: 6 results) Book (2 results)

  • [Journal Article] Polymer-conjugated glucosamine complexed with boric acid shows tumor-selective accumulation and simultaneous inhibition of glycolysis2021

    • Author(s)
      Islam Waliul、Matsumoto Yoshitaka、Fang Jun、Harada Ayaka、Niidome Takuro、Ono Katsuhiko、Tsutsuki Hiroyasu、Sawa Tomohiro、Imamura Takahisa、Sakurai Kazuo、Fukumitsu Nobuyoshi、Yamamoto Hirofumi、Maeda Hiroshi
    • Journal Title

      Biomaterials

      Volume: 269 Pages: 120631-120631

    • DOI

      10.1016/j.biomaterials.2020.120631

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Non-isotope enriched phenylboronic acid-decorated dual-functional nano-assembles for an actively targeting BNCT drug2021

    • Author(s)
      Kim, A. Suzuki, M. Matsumoto, Y. Fukumitsu, N. Nagasaki, Y.
    • Journal Title

      Biomaterials

      Volume: 268 Pages: 120551-120551

    • DOI

      10.1016/j.biomaterials.2020.120551

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] シアル酸過剰発現腫瘍に対して優れたBNCT治療効果を発揮するフェニルボロン酸修飾高分子ナノ粒子の開発2021

    • Author(s)
      松本孔貴, 金雅覽, 鈴木実, 福光延吉, 櫻井英幸
    • Journal Title

      化学工業

      Volume: 72 Pages: 230-237

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Folate-appended cyclodextrin improves the intratumoral accumulation of existing boron compounds2020

    • Author(s)
      Matsumoto, Y. Hattori, K. Arima, H. Motoyama, K. Higashi, T. Ishikawa, H. Fukumitsu, N. Aihara, T. Nakai, K. Kumada, H. Sakurai, H.
    • Journal Title

      Appl Radiat Isot

      Volume: 163 Pages: 109201-109201

    • DOI

      10.1016/j.apradiso.2020.109201

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers2020

    • Author(s)
      Vares, G. Jallet, V. Matsumoto, Y. Rentier, C. Takayama, K. Sasaki, T. Hayashi, Y. Kumada, H. Sugawara, H.
    • Journal Title

      Nanomedicine

      Volume: 27 Pages: 102195-102195

    • DOI

      10.1016/j.nano.2020.102195

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of RhoA overexpression on clinical outcomes in cervical squamous cell carcinoma treated with concurrent chemoradiotherapy2020

    • Author(s)
      Tanaka Keiichi、Matsumoto Yoshitaka、Ishikawa Hitoshi、Fukumitsu Nobuyoshi、Numajiri Haruko、Murofushi Keiko、Oshiro Yoshiko、Okumura Toshiyuki、Satoh Toyomi、Sakurai Hideyuki
    • Journal Title

      Journal of Radiation Research

      Volume: 61 Issue: 2 Pages: 221-230

    • DOI

      10.1093/jrr/rrz093

    • NAID

      120007166910

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relative Biological Effectiveness and Fractionation of Proton-Beam Therapy2020

    • Author(s)
      Matsumoto Yoshitaka
    • Journal Title

      Proton Beam Radiotherapy: Physics and Biology

      Volume: - Pages: 209-222

    • DOI

      10.1007/978-981-13-7454-8_16

    • ISBN
      9789811374531, 9789811374548
    • Related Report
      2019 Research-status Report
  • [Journal Article] 8.2.7 Metastasis of Cancer from the viewpoint of radiation therapy—Anti-Metastatic Effects of High LET Particle Beam—2019

    • Author(s)
      Matsumoto Yoshitaka
    • Journal Title

      RADIOISOTOPES

      Volume: 68 Issue: 10 Pages: 731-740

    • DOI

      10.3769/radioisotopes.68.731

    • NAID

      130007728651

    • ISSN
      0033-8303, 1884-4111
    • Year and Date
      2019-10-15
    • Related Report
      2019 Research-status Report
  • [Journal Article] Estimation of RBE values for carbon-ion beams in the wide dose range using multicellular spheroids2019

    • Author(s)
      Yoshitaka Matsumoto, Yoshiya Furusawa, Mizuho Aoki-Nakano, Naruhiro Matsufuji, Ryoichi Hirayama, Tatsuaki Kanai, Koichi Ando and Hideyuki Sakurai
    • Journal Title

      Radiation Protection Dosimetry

      Volume: in press Issue: 1-2 Pages: 45-49

    • DOI

      10.1093/rpd/ncy269

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] DOSE-RATE AND CELL-KILLING SENSITIVITY OF HIGH-LINEAR ENERGY TRANSFER ION BEAM2019

    • Author(s)
      Furusawa Yoshiya、Matsumoto Yoshitaka、Hirayama Ryoichi、Ohsawa Daisuke、Konishi Teruaki
    • Journal Title

      Radiation Protection Dosimetry

      Volume: 183 Issue: 1-2 Pages: 219-222

    • DOI

      10.1093/rpd/ncy267

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Beam performance of the iBNCT as a compact linac-based BNCT neutron source developed by University of Tsukuba2019

    • Author(s)
      Kumada Hiroaki、Takada Kenta、Naito Fujio、Kurihara Toshikazu、Sugimura Takashi、Matsumoto Yoshitaka、Sakurai Hideyuki、Matsumura Akira、Sakae Takeji
    • Journal Title

      AIP Conference Proceedings

      Volume: 2160 Pages: 1-10

    • DOI

      10.1063/1.5127705

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DIFFERENCE IN DEGREE OF SUB-LETHAL DAMAGE RECOVERY BETWEEN CLINICAL PROTON BEAMS AND X-RAYS2018

    • Author(s)
      Matsumoto Yoshitaka、Ando Koichi、Kato Takamitsu A、Sekino Yuta、Ishikawa Hitoshi、Sakae Takeji、Tsuboi Koji、Sakurai Hideyuki
    • Journal Title

      Radiation Protection Dosimetry

      Volume: 183 Issue: 1-2 Pages: 93-97

    • DOI

      10.1093/rpd/ncy270

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antimetastatic effects of carbon-ion beams on malignant melanomas2018

    • Author(s)
      Yoshitaka Matsumoto, Yoshiya Furusawa, Akiko Uzawa, Ryoichi Hirayama, Sachiko Koike, Koichi Ando, Koji Tsuboi and Hideyuki Sakurai
    • Journal Title

      Radiation Research

      Volume: 190 Issue: 4 Pages: 412-423

    • DOI

      10.1667/rr15075.1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers2018

    • Author(s)
      Guillaume Vares, Vincent Jallet, Yoshitaka Matsumoto, Cedric Rentier, Kentaro Takayama, Toshio Sasaki, Yoshio Hayashi, Hiroaki Kumada, Hirotaka Sugawara
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/471128

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Commissioning status of the linac for the iBNCT project2018

    • Author(s)
      Masaharu Sato, Yoshitaka Matsumoto, et al
    • Journal Title

      LINAC2018 Proccedings

      Volume: 1 Pages: 174-176

    • DOI

      10.18429/JACOW-LINAC2018-MOPO082

    • Related Report
      2018 Research-status Report
  • [Presentation] フェニルボロン酸修飾高分子ナノ粒子はシアル酸過剰発現B16メラノーマに対して優れたBNCT治療効果を発揮する2020

    • Author(s)
      松本孔貴, 金雅覽, 鈴木実, 福光延吉, 櫻井英幸
    • Organizer
      日本放射線影響学会第63回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] In vivo evaluation of a phenylboronic acid-installed, actively targeted novel BNCT agent against melanoma-bearing mouse model2020

    • Author(s)
      Yoshitaka Matsumoto, Ahram Kin, Nobuyoshi Fukumitsu, Minoru Suzuki, Yukio Nagasaki and Hideyuki Sakurai
    • Organizer
      PTCOG online meeting 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Polymer conjugated glucosamine complexed with boric acid with tumor selective accumulation and simultaneous inhibition of glycolysis2020

    • Author(s)
      Islam Waliul、松本孔貴、原田彩花、方軍、澤智裕、新留琢郎、福光延吉、 前田浩
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 放射線治療用金ナノ粒子増感剤による腫瘍免疫誘導とその評価2020

    • Author(s)
      三澤雅樹、松本孔貴、沼野智一、新田尚隆、岡田朋子、余語克紀
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Targeting hypersialyated B16 melanoma using a phenylboronic acid-installed polymeric nanoparticle towards a novel BNCT agent2020

    • Author(s)
      Ahram Kim, Minoru Suzuki, Yoshitaka Matsumoto, Nobuyoshi Fukumitsu, Yukio Nagasaki
    • Organizer
      第69回高分子学会年次大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] iBNCT 加速器の現状報告 20192019

    • Author(s)
      杉村高志、池上清、帯名崇、久保田親、 栗原俊一、小林仁、佐藤将春、柴田崇統、高木昭、高崎栄一、内藤富士雄、南茂今朝雄 、方志高、福井祐治、福田将史、二ツ川健太、本田洋介、三浦太一、宮島司、熊田博明、田中進、名倉信明、松本孔貴、大場俊幸、小林 武、堀 利彦、矢部 伸浩、山口 晃典、櫻山久志、豊島寿一、吉沢寿夫、長谷川和男
    • Organizer
      16th Annual Meeting of Particle Accelerator Society of Japan
    • Related Report
      2019 Research-status Report
  • [Presentation] 温水還流加温と比較して、低出力温熱治療(オンコサーミア)は効率的な殺細胞効果と放射線増感効果を示す2019

    • Author(s)
      松本孔貴、菅原裕、関野雄太、福光延吉、石川仁、櫻井英幸
    • Organizer
      第22回癌治療増感研究シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 最新の粒子線治療との相乗効果を目指したマテリアル開発2019

    • Author(s)
      松本孔貴
    • Organizer
      つくば医工連携フォーラム2020 医工連携から社会実装・スタートアップへ
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] In vivo evaluation of a phenylboronic acid-installed, activity targeted novel BNCT agent against B16 melanoma-bearing mouse model2019

    • Author(s)
      Yoshitaka Matsumoto, Kim Ahram, Nobuyoshi Fukumitsu, Minoru Suzuki, Yukio Nagasaki and Hideyuki Sakurai
    • Organizer
      3rd NTUーUT Radiation Oncology Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Dose rate effect ~from classical low dose rate effect to Flash therapy~2019

    • Author(s)
      Yoshitaka Matsumoto
    • Organizer
      Hitachi Users Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Non-clinical trial of iBNCT2019

    • Author(s)
      Yoshitaka Matsumoto
    • Organizer
      Seminar of Boron Neutron Capture Therapy in Korea
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 温水還流加温と比較して、低出力温熱治療(オンコサーミア)は効率的な殺細胞効果と放射線増感効果を示す2019

    • Author(s)
      松本孔貴、林淳子、関野雄太、福光延吉、斎藤高、石川仁、櫻井英幸
    • Organizer
      日本ハイパーサーミア学会第36回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 第5回臨床家にも理解る放射線生物学~温熱はどうしてがん治療に有効なのか?~2019

    • Author(s)
      松本孔貴
    • Organizer
      第7回つくば放射線治療を学ぼう会
    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] Evaluation of phenylboronic acid-installed polymeric nanoparticle as an actively targeted BNCT agent against a syngeneic melanoma model2019

    • Author(s)
      Yoshitaka Matsumoto, Kim Ahram, Minoru Suzuki, Nobuyoshi Fukumitsu, Yukio Nagasaki and Hideyuki Sakurai
    • Organizer
      第22回癌治療増感研究シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] B16メラノーマ担持マウスモデルを用いたフェニルボロン酸修飾シアル酸ターゲティング新規BNCT剤の評価2019

    • Author(s)
      松本孔貴、金雅覽、福光延吉、鈴木実、長崎幸夫、櫻井英幸
    • Organizer
      日本放射線影響学会第62回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Evaluation of a phenylboronic acid-decorated, sialic acid-targeting novel BNCT agent against B16 melanoma-bearing mouse mode2019

    • Author(s)
      Yoshitaka Matsumoto, Kim Ahram, Nobuyoshi Fukumitsu, Minoru Suzuki, Yukio Nagasaki and Hideyuki Sakurai
    • Organizer
      The 10th Young Researchers BNCT Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Folate-modified cyclodextrin improved the active tumor accumulation of BSH and showed a strong therapeutic effect of BNCT2019

    • Author(s)
      Yoshitaka Matsumoto,Kenjiro Hattori, Hidetoshi Arima, Keiichi Motoyama, Taishi Higashi, Nobuyoshi Fukumitsu, Teruhito Aihara, Hitoshi Ishikawa, Hiroaki Kumada and Hideyuki Sakurai
    • Organizer
      PTCOG 58 Scientific Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of uneven fractionation using high LET carbon-ion beams for tumor metastatic abilities2018

    • Author(s)
      Yoshitaka MATSUMOTO, Yoshiya FURUSAWA, Huizi LI, Ryoichi HIRAYAMA, Akiko UZAWA, Koichi ANDO, Shin-ichiro MASUNAGA, Koji TSUBOI and Hideyuki SAKURAI
    • Organizer
      ISIT2018 International Symposium on Ion Therapy 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 陽子線治療と抗がん剤の併用効果の検証~従来法と新規イメージングシステムの比較~2018

    • Author(s)
      松本孔貴,斎藤高,関野雄太,石川仁,榮武二,坪井康次,櫻井英幸
    • Organizer
      日本動物実験代替法学会 第31回大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Folate-modified cyclodextrin improves the intratumoral accumulation of existing boron compounds.2018

    • Author(s)
      Yoshitaka MATSUMOTO,Kenjiro HATTORI、HidetoshiARIMA、Keiichi MOTOYAMA、Taishi AZUMA、Hitoshi ISHIKAWA、Nobuyoshi FUKUMITSU、Teruhito AIHARA,Hiroaki, KUMADA, Koji TSUBOI and Hideyuki SAKURAI
    • Organizer
      ICNCT18 18th International Congress on Neutron Capture Therapy
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Difference in SLDR and DNA damage repair after split-irradiation with proton beams and X-rays.2018

    • Author(s)
      Yoshitaka Matsumoto, Koichi Ando, Takamitsu A Kato, Yuta Sekino, Takeji Sakae, Koji Tsuboi and Hideyuki Sakurai
    • Organizer
      PTCOG 57 Scientific Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規温熱治療オンコサーミアと放射線の併用による抗腫瘍効果2018

    • Author(s)
      松本孔貴,林淳子,関野雄太,福光延吉,斎藤高,石川仁,櫻井英幸
    • Organizer
      第47回放射線による制癌シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 放射線の生物効果における量と質と線量投与時期~細胞致死と転移抑制から~2018

    • Author(s)
      松本孔貴,古澤佳也、平山亮一、鵜澤玲子、増永慎一郎、安藤興一、榮武二、石川仁、坪井康次、 櫻井英幸
    • Organizer
      第21回 癌治療増感研究シンポジウム
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Commissioning status of the linac for the iBNCT project2018

    • Author(s)
      Masaharu Sato, Yoshitaka Matsumoto, et al
    • Organizer
      29th Linear Accelerator Conference-LINAC18
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] Proton Beam Radiotherapy: Physics and Biology (English Edition) 1st ed.2020

    • Author(s)
      Koji Tsuboi, Takeji Sakae, Ariungerel Gerelchuluun, Kiyoshi Yasuoka, Yutaro Mori, Hideyuki Takei, Tatsuhiko Sato, Kenta Takada, Hiroaki Kumada, Toshiyuki Terunuma, Satoshi Kamizawa, Lue Sun, Yoshitaka Matsumoto
    • Total Pages
      235
    • Publisher
      Springer
    • ISBN
      9789811374548
    • Related Report
      2020 Annual Research Report
  • [Book] やさしくわかる放射線治療学2018

    • Author(s)
      松本孔貴 他28名
    • Total Pages
      5
    • Publisher
      株式会社 学研メディカル秀潤社
    • ISBN
      9784780909753
    • Related Report
      2018 Research-status Report

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

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