Development and Validation of Safe and Efficient Multi-functional Boron Nanoformulation for Next-generation BNCT
| Project/Area Number |
18K07256
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
長崎 幸夫 筑波大学, 数理物質系, 教授 (90198309)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(41 results)
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[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.
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Journal Title
Appl Radiat Isot
Volume: 163
Pages: 109201-109201
DOI
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Peer Reviewed
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[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
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[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
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