Development of cancer specific Gd neutron capture therapy using membrane fusion protein & nuclear locarization signal

• Project/Area Number: 25670571
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Yanagie Hironobu 東京大学, 工学(系)研究科(研究院), 研究員 (30212278)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Hiroyuki 東京大学, 大学院工学系研究科(工学部), 教授 (70216753)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ガドリニウム化合物 / 中性子捕捉療法 / Drug Delivery System / ナノミセル / ポリエチレングリコール / リン酸カルシウム / ポリエチレンイミン / 膜融合ペプチド / ガドニウム化合物 / Drug delivery System / ＪＴＳ－１

Outline of Final Research Achievements

Cancer cell cytotoxicity was obtained by gamma ray and auger electron derived the reaction between Gadolinium(Gd) and thermal neutron in Gd neutron capture therapy(NCT). It is necessary to accumulate the Gd atoms in the cancer cell, especially, in nucleus, for selective damage to cancer cells without the affect to neighbor normal tissues, so it is important to develop the Drug Delivery System.
We prepared Gadoteridol entrapped poly-cationized-calcium phosphate nano micelle coating with polyethylene glycol (Ca-P nano micelle). Gd concentration in tumour was keeping higher compare to original Gd solution until 24hrs after intraveneous injection(IV). After IV injection of Gd Ca-P nano micelle, 50 % of tumour growth suppression was shown in Colon 26 mouse subcutaneous tumour model with thermal neutron irradiation at Kyoto University Research Reactor Institute. We hope to develop the Gd NCT as selective novel cancer therapy.

Research Products

• [Journal Article] In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent (2016)
  • Author(s): Novriana Dewi, Peng Mi, Hironobu Yanagie, Yuriko Sakurai, Yasuyuki Morishita, Masashi Yanagawa, Takayuki Nakagawa, Atsuko Shinohara, Takehisa Matsukawa, Kazuhito Yokoyama, Horacio Cabral, Minoru Suzuki, Yoshinori Sakurai, Hiroki Tanaka, Koji Ono, Nobuhiro Nishiyama, Kazunori Kataoka, Hiroyuki Takahashi
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 142 Issue: 4 Pages: 767-775
  • DOI: 10.1007/s00432-015-2085-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agen (2013)
  • Author(s): N. Dewi, H. Yanagie, H. Zhu, K. Demachi, A. Shinohara, K. Yokoyama, M. Sekino, Y. Sakurai, Y. Morishita, N. Iyomotog, T. Nagasaki, Y. Horiguchi, Y. Nagasaki, J. Nakajima, K. Ono, K.Kakimi, H.Takahashi
  • Journal Title: Biomed. Biopharmacother. Volume: 67 Issue: 6 Pages: 451-457
  • DOI: 10.1016/j.biopha.2012.11.010
  • Peer Reviewed
• [Presentation] Tumour growth suppression by gadolinium capture therapy with multipleinjections of Gd-DTPA-containing calcium phosphate-based nanoparticles (2015)
  • Author(s): Dewi N, Yanagie H,Takahashi H,et al
  • Organizer: 8th Young Researchers’ BNCT Meeting
  • Place of Presentation: Pavia,Italy
  • Year and Date: 2015-09-16
• [Presentation] In vivo evaluation of gadolinium neutron capture therapy effectivity with multiple injections of calcium phosphate-based nanoparticles incorporating Gd-DTPA (2015)
  • Author(s): Dewi N, Yanagie H,Takahashi H,et al
  • Organizer: 12th Congress on Neutron Capture Therapy
  • Place of Presentation: Kobe Gakuin University,Kobe,JAPAN
  • Year and Date: 2015-09-04
• [Presentation] Tumor growth suppression by neutron capture therapy using Gd-DTPA-incorporated calcium phosphate nanoparticles as gadolinium drug agent (2014)
  • Author(s): Novriana Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 第11回日本中性子捕捉療法学会
  • Place of Presentation: 大阪大学 大阪
  • Year and Date: 2014-07-05 – 2014-07-06
• [Presentation] In vivo evaluation of Gd-DTPA-incorporated calcium phosphate nanoparticles for neutron capture therapy agent (2014)
  • Author(s): N. Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 16th International Conference on Neutron Capture Therapy
  • Place of Presentation: Helsinki, FINLAND
  • Year and Date: 2014-06-14 – 2014-06-19
• [Presentation] 中性子捕捉療法のがん治療への応用展開 (2014)
  • Author(s): 柳衛宏宣
  • Organizer: FIRST Joint International Symposium
  • Place of Presentation: 東京大学 東京
  • Invited
• [Presentation] Application of Liposomal Gadolinium Delivery in Neutron Capture (2013)
  • Author(s): Novriana Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 第10回日本中性子捕捉療法学会学術大会
  • Place of Presentation: 岡山県岡山市
• [Presentation] Application of Gadolinium Drug Delivery in Neutron Capture Therapy: (2013)
  • Author(s): Novriana Dewi, Yanagie H, Takahashi H.,et al.
  • Organizer: 7th Young Researchers Meeting on NCT
  • Place of Presentation: Granada, Spain
• [Presentation] 集学的癌治療に向けた中性子捕捉療法の応用展開
  • Author(s): 柳衛宏宣
  • Organizer: 明治薬科大学 がんプロフェッショナル養成基盤推進事業講演会
  • Place of Presentation: 東京都清瀬市
  • Invited