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Development of intracellular targeting liposomes for boron neutron-capture therapy

Research Project

Project/Area Number 13470190
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionTeikyo University

Principal Investigator

MARUYAMA Kazuo  Teikyo University, School of Pharmaceutical Science, Professor, 薬学部, 教授 (30130040)

Co-Investigator(Kenkyū-buntansha) YANAGIE Hironobu  University of Tokyo, RCAST, Associate Professor, 先端科学技術センター, 助教授 (30212278)
KASAOKA Satoshi  Teikyo University, School of Pharmaceutical Science, Research Instructor, 薬学部, 助手 (90338690)
TAKIZAWA Tomoko  Teikyo University, School of Pharmaceutical Science, Research Instructor, 薬学部, 助手 (90260934)
ONO Koji  Kyoto University, Institute For Atomic Reactor, Professor, 原子炉実験場, 教授 (90122407)
SHINOHARA Atsuko  Juntendo University School of Medicine, Assistant Professor, 医学部, 講師 (90157850)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥7,900,000 (Direct Cost: ¥7,900,000)
KeywordsNeutron-Capture Therapy / DDS / Liposome / Transferrin
Research Abstract

The successful treatment of cancer by BNCT requires the selective concentration of ^<10>B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of ^<10>B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vitro, and were internalized by receptor-mediated endocytosis. ^<10>B-PEG-liposomes and ^<10>B-TF-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of ^<10>B content in tumor. After thermal neutron irradiation of mice injected with ^<10>B-PEG-liposomes or ^<10>B-TF-liposomes, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of ^<10>B TF-PEG-liposome can increase the intracellular retention of ^<10>B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] O.Ishida, et al.: "Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo."Pharm.Res.. 18. 1042-1048 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ogura, et al.: "Neutron capture autoradiography for a study on boron neutron capture therapy."Radiation Measurement. 34. 555-558 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Iinuma, et al.: "Intracellular Targeting Therapy of Cisplatin-Encapsulated Transferrin-PEG- Liposome on Peritoneal Dissemination of Gastric Cancer."Int.J.Cancer. 99. 130-137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Mizoue, et al.: "Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells."Int.J.Pharm.. 237. 129-137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Omori, et al.: "Targeting of post-ischemic cerebral endothelium in rat by liposomes bearing polyethylene glycol-coupled transferrin."Neurol.Res.. 25. 275-279 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kazuo Maruyama et al.: "Intracellular Targeting of Sodium Mercaptoundecahydrodo decaborate (BSH) to Solid Tumors by Transferrin-PEG Liposomes, for Boron Neutron-Capture Therapy (BNCT)."J.Controlled Release. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] O.Ishida, et al.: "Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo"Pharm. Res.. 18(7). 1042-1048 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ogura, et al.: "Neutron capture autoradiography for a study on boron neutron capture therapy"Radiation Measurement. 34. 555-558 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Tinuma, et al.: "Intracellular Targeting Therapy of Cisplatin-Encapsulated Transferrin-PEG-Liposome on Peritoneal Dissemination of Gastric Cancer"Int. J. Cancer. 99. 130-138 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Mizoue, et al.: "Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells"Int. J. Pharm.. 237. 129-137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] N.Omori, et al.: "Targeting of post-ischemic cerebral endothelium in rat by liposomes bearing polyethylene glycol-coupled transferrin"Neurol. Res.. 25. 275-279 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Maruyama, et al.: "Intracellular Targeting of Sodium Mercaptoundecahydro dodecaborate (BSH) to Solid Tumors by Transferrin-PEG Liposomes, for Boron Neutron-Capture Therapy (BNCT)"J. Controlled Release. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Iinuma, et al.: "Intracellular Targeting Therapy of Cisplatin-Encapsulated Transferrin-PEG- Liposome on Peritoneal Dissemination of Gastric Cancer."Int.J.Cancer. 99. 130-137 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Mizoue, et al.: "Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells."Int.J.Pharm.. 237. 129-137 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Omori, et al.: "Targeting of post-ischemic cerebral endothelium in rat by liposomes bearing polyethylene glycol-coupled transferrin."Neurol.Res.. 25. 275-279 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Intracellular Targeting of Sodium Mercaptoundecahydrodo decaborate (BSH) to Solid Tumors by Transferrin-PEG Liposomes, for Boron Neutron-Capture Therapy (BNCT)."J.Controlled Release. (In press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Targeting of post-ischemic cerebral endothelium in rat by liposomes bearing polyethylene glycol-coupled transferrin"Neurol.Res.. (印刷中). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunollposomes to tumor cells"Int.J.Pharm.. 237. 129-137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Intracellular Targeting Therapy of Cisplatin-Encapsulated Transferrin-PEG-Liposome on Peritoneal Dissemination of Gastric Cancer"Int.J.Cancer. 99. 130-137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Neutron capture autoradiography for a study on boron neutron capture therapy"Radiation Measurement. 34. 555-558 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "p21(Cip-1/sdl-1/WAF-1) gene is involved in chondrogenic differentiation of ATDC5 cells in vitro"J.Biol.Chem.. 276. 33249-33256 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Three-dimensional morphological analysis of antigen-antibody reaction in hepatic sinusoids preserved in hypothermic UW solution"Cryobiology. 42. 145-150 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuo Maruyama et al.: "Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo"Pharm.Res.. 18. 1042-1048 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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