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Development of metabolism-controlled boron delivery systems exerting quick tumor-selective accumulation and retention

Research Project

Project/Area Number 18K18383
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionTokyo Institute of Technology

Principal Investigator

Nomoto Takahiro  東京工業大学, 科学技術創成研究院, 助教 (00734732)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords薬物送達システム / 中性子捕捉療法 / 高分子 / ボロノフェニルアラニン / LAT1 / アミノ酸トランスポーター / 高分子コンジュゲート / ホウ素デリバリー / 機能性高分子 / 生体適合性高分子
Outline of Final Research Achievements

In boron neutron capture therapy (BNCT), boronophenylalanine (BPA) has been one of the most clinically studied boron drugs. Since BPA is taken up via the LAT1 amino acid transporter overexpressed on many cancer cells, it can selectively accumulate within tumors. However, it cannot retain in the target tumor cells for a long time, which sometimes compromises its BNCT effect. In this research project, in order to improve the retention of BPA in tumors, we have developed functional polymers that can form boronate esters with multiple BPA molecules in the side chain. This study clarified that the functional polymers dramatically improved the retention of BPA in tumors and significantly enhanced the BNCT effect.

Academic Significance and Societal Importance of the Research Achievements

BNCTはホウ素原子と熱中性子の核反応により生じるアルファ粒子とリチウム反跳核によりがん細胞を選択的に殺傷する方法である。BNCTの適用範囲を拡大するためには、腫瘍に選択的に集積し、熱中性子照射中に高い腫瘍内ホウ素濃度を維持することのできるホウ素薬剤を開発することが重要である。本研究では、既存のホウ素薬剤boronophenylalanine(BPA)に水中で加えるだけでその腫瘍集積性と滞留性を劇的に向上し、治療効果も大幅に向上することのできる機能性高分子を開発した。本研究成果により、BNCTのさらなる発展が期待できる。

Report

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

    (37 results)

All 2021 2020 2019 2018 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 3 results) Presentation (20 results) (of which Int'l Joint Research: 10 results,  Invited: 6 results) Remarks (4 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Fructose-functionalized polymers to enhance therapeutic potential of p-boronophenylalanine for neutron capture therapy2021

    • Author(s)
      Nomoto Takahiro、Yao Ying、Inoue Yukiya、Suzuki Minoru、Kanamori Kaito、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Journal of Controlled Release

      Volume: 332 Pages: 184-193

    • DOI

      10.1016/j.jconrel.2021.02.021

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential Self-Assembly Using Tannic Acid and Phenylboronic Acid-Modified Copolymers for Potential Protein Delivery2020

    • Author(s)
      Honda Yuto、Nomoto Takahiro、Matsui Makoto、Takemoto Hiroyasu、Kaihara Yuka、Miura Yutaka、Nishiyama Nobuhiro
    • Journal Title

      Biomacromolecules

      Volume: 21 Issue: 9 Pages: 3826-3835

    • DOI

      10.1021/acs.biomac.0c00903

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poly(vinyl alcohol) boosting therapeutic potential of p-boronophenylalanine in neutron capture therapy by modulating metabolism2020

    • Author(s)
      Nomoto Takahiro、Inoue Yukiya、Yao Ying、Suzuki Minoru、Kanamori Kaito、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Science Advances

      Volume: 6 Issue: 4

    • DOI

      10.1126/sciadv.aaz1722

    • NAID

      120006779811

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ring-Fused Firefly Luciferins: Expanded Palette of Near-Infrared Emitting Bioluminescent Substrates2020

    • Author(s)
      Ikeda Yuma、Nomoto Takahiro、Hiruta Yuki、Nishiyama Nobuhiro、Citterio Daniel
    • Journal Title

      Analytical Chemistry

      Volume: 92 Issue: 6 Pages: 4235-4243

    • DOI

      10.1021/acs.analchem.9b04562

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Polymeric modification of gemcitabine via cyclic acetal linkage for enhanced anticancer potency with negligible side effects2020

    • Author(s)
      Takemoto Hiroyasu、Inaba Takanori、Nomoto Takahiro、Matsui Makoto、Liu Xiaomeng、Toyoda Masahiro、Honda Yuto、Taniwaki Kaori、Yamada Naoki、Kim Junhyun、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Biomaterials

      Volume: 235 Pages: 119804-119804

    • DOI

      10.1016/j.biomaterials.2020.119804

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pyruvate Responsiveness Based on α-Oxohydrazone Formation for Intracellular siRNA Release from Polyion Complex-Based Carriers2019

    • Author(s)
      Takemoto Hiroyasu、Wang Chih-Ling、Nomoto Takahiro、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Biomacromolecules

      Volume: 20 Issue: 6 Pages: 2305-2314

    • DOI

      10.1021/acs.biomac.9b00261

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers2019

    • Author(s)
      Watanabe Sumiyo、Hayashi Kotaro、Toh Kazuko、Kim Hyun Jin、Liu Xueying、Chaya Hiroyuki、Fukushima Shigeto、Katsushima Keisuke、Kondo Yutaka、Uchida Satoshi、Ogura Satomi、Nomoto Takahiro、et al.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1894-1894

    • DOI

      10.1038/s41467-019-09856-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Poly(N-isopropylacrylamide)-Based Polymer-Inducing Isothermal Hydrophilic-to-Hydrophobic Phase Transition via Detachment of Hydrophilic Acid-Labile Moiety2018

    • Author(s)
      Muttaqien Sjaikhurrizal El、Nomoto Takahiro、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Biomacromolecules

      Volume: 20 Issue: 4 Pages: 1493-1504

    • DOI

      10.1021/acs.biomac.8b01465

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers2018

    • Author(s)
      Dou Xuebo、Nomoto Takahiro、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8126-8126

    • DOI

      10.1038/s41598-018-26593-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epirubicin-loaded polymeric micelles effectively treat axillary lymph nodes metastasis of breast cancer through selective accumulation and pH-triggered drug release2018

    • Author(s)
      Chida Tsukasa、Miura Yutaka、Cabral Horacio、Nomoto Takahiro、Kataoka Kazunori、Nishiyama Nobuhiro
    • Journal Title

      Journal of Controlled Release

      Volume: 292 Pages: 130-140

    • DOI

      10.1016/j.jconrel.2018.10.035

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 超低侵襲ケミカルサージェリーを目指した高分子コンジュゲート型DDSの設計2021

    • Author(s)
      野本貴大
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Drug delivery using functional polymer-conjugates2021

    • Author(s)
      Takahiro Nomoto
    • Organizer
      Topical Meeting on Condensed-Matter Chemistry on Actinides
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Development of functional polymers to boost therapeutic potential of boronophenylalanine in neutron capture therapy2020

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Kaito Kanamori, Kakeru Konarita, Hiroyasu Takemoto, Makoto Matsui, Nobuhiro Nishiyama
    • Organizer
      第69回高分子討論会
    • Related Report
      2020 Annual Research Report
  • [Presentation] タンニン酸とボロン酸ケミストリーを利用した高分子複合体の簡便調製法2020

    • Author(s)
      野本貴大、本田雄士、海原悠可、喜納宏昭、武元宏泰、松井誠、西山伸宏
    • Organizer
      第3回COI学術交流会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ポリビニルアルコールを利用したホウ素中性子捕捉療法の治療効果向上2020

    • Author(s)
      野本貴大
    • Organizer
      日本放射線影響学会第63回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 代謝制御型ドラッグデリバリーシステムによるホウ素中性子捕捉療法2020

    • Author(s)
      野本貴大
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Poly(vinyl alcohol) for enhancing therapeutic effects of p-boronophenylalanine in neutron capture therapy2020

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Kaito Kanamori, Hiroyasu Takemoto, Makoto Matsui, Nobuhiro Nishiyama
    • Organizer
      The International Symposium on Biomedical Materials for Drug/Gene Delivery
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photosensitizer delivery to tumor cells and tumor-associated vasculature using functional polymers2019

    • Author(s)
      Takahiro Nomoto, Xuebo Dou, Hiroyasu Takemoto, Makoto Matsui, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      7th International ALA and Porphyrin Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Boosting therapeutic potential of p-boronophenylalanine using biocompatible polymers2019

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Kaito Kanamori, Hiroyasu Takemoto, Makoto Matsui, Nobuhiro Nishiyama
    • Organizer
      yBNCT 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Metabolism-controlled boron delivery systems composed of biocompatible polymers and boronophenylalanine for neutron capture therapy2019

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Kaito Kanamori, Hiroyasu Takemoto, Makoto Matsui, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      The ACS Spring 2019 National Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photodynamic therapy using functional polymers targeting tumor microenvironment2019

    • Author(s)
      Takahiro Nomoto
    • Organizer
      The 3rd Workshop for Japan-Korea Young Scientists on Pharmaceutics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Photodynamic therapy utilizing functional polymers that exert pH-responsive isothermal phase transition2019

    • Author(s)
      3.Takahiro Nomoto, Sjaikhurrizal El Muttaqien, Hiroyasu Takemoto, Makoto Matsui, Nobuhiro Nishiyama
    • Organizer
      ICPST-36
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体適合性高分子とp-boronophenylalanineから構成されるホウ素送達システムの開発と構成高分子の物性が体内動態と治療効果に与える影響に関する考察2019

    • Author(s)
      野本貴大、井上透矢、Yao Ying、鈴木実、金盛開人、武元宏泰、松井誠、友田敬士郎、西山伸宏
    • 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] 生体適合性高分子とボロノフェニルアラニンから構成される中性子捕捉療法用代謝制御型ホウ素送達システム2019

    • Author(s)
      野本貴大、井上透矢、Yao Ying、鈴木実、金盛開人、武元宏泰、松井誠、西山伸宏
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Metabolism-controlled boron delivery systems for neutron capture therapy2019

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Kaito Kanamori, Hiroyasu Takemoto, Makoto Matsui, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      2019 International Symposium on Nanotechnology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Metabolism-controlled boron delivery systems composed of boronophenylalanine and functional polymers for neutron capture therapy2018

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Kaito Kanamori, Hiroyasu Takemoto, Makoto Matsui, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      The 12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Metabolism-controlled boron delivery systems composed of p-boronophenylalanine and poly(vinyl alcohol)2018

    • Author(s)
      Takahiro Nomoto, Yukiya Inoue, Ying Yao, Minoru Suzuki, Hiroyasu Takemoto, Makoto Matsui, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      18th International Congress on Neutron Capture Therapy
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhanced tumor-targeted delivery of p-boronophenylalanine using fructose-functionalized polymers for boron neutron capture therapy2018

    • Author(s)
      Ying Yao, Takahiro Nomoto, Yukiya Inoue, Minoru Suzuki, Makoto Matsui, Hiroyasu Takemoto, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      18th International Congress on Neutron Capture Therapy
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生体適合性機能性高分子によるボロノフェニルアラニンの代謝制御と治療効果の向上2018

    • Author(s)
      野本貴大、井上透矢、Yao Ying、鈴木実、金盛開人、武元宏泰、松井誠、友田敬士郎、西山伸宏
    • 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] Tumor-targeted delivery of BPA using functional polymers for boron neutron capture therapy2018

    • Author(s)
      Yao Ying、野本貴大、井上透矢、鈴木実、武元宏泰、松井誠、友田敬士郎、西山伸宏
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] スライムの化学でがん治療の幅をひろげる ホウ素中性子捕捉療法の効果アップ

    • URL

      https://www.titech.ac.jp/news/2020/046337.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 「スライムの化学」を利用した第5のがん治療法

    • URL

      https://www.titech.ac.jp/news/2020/046060.html

    • Related Report
      2019 Research-status Report
  • [Remarks] Using slime chemistry to improve cancer treatment

    • URL

      https://www.titech.ac.jp/english/news/2020/046341.html

    • Related Report
      2019 Research-status Report
  • [Remarks] How to keep boron inside cells during radiotherapy

    • URL

      https://www.titech.ac.jp/english/news/2020/046117.html

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] タンパク質複合体、医薬、癌治療剤、及びキット2019

    • Inventor(s)
      野本貴大、本田雄士、西山伸宏、武元宏泰、松井誠
    • Industrial Property Rights Holder
      東京工業大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-100395
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 結合体、及び癌治療剤2019

    • Inventor(s)
      野本貴大、西山伸宏、河本花奈、武元宏泰、松井誠
    • Industrial Property Rights Holder
      東京工業大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-083250
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] p-ボロノフェニルアラニン誘導体及びそれを含む組成物、並びにそれらを製造するためのキット2019

    • Inventor(s)
      西山伸宏、野本貴大、井上透矢、ヤオイン、金盛開人、他
    • Industrial Property Rights Holder
      東京工業大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

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

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