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ナノテクノロジーを用いた薬剤投与システムの開発による消化器癌の新しい治療戦略

Research Project

Project/Area Number 18659080
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionFujita Health University

Principal Investigator

土田 邦博  Fujita Health University, 総合医科学研究所, 教授 (30281091)

Co-Investigator(Kenkyū-buntansha) 村上 達也  藤田保健衛生大学, 総合医科学研究所, 助教 (90410737)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsナノメディシン / ドラッグデリバリーシステム / 抗がん剤 / 光線力学療法 / 温熱療法 / 転移リンパ節 / センチネルリンパ節 / ドラッグデリバリー / 担がんマウス / がん転移 / ナノテクノロジー / 消化器癌 / リンパ節転移
Research Abstract

カーボンナノホーン(CNH)は先端の閉じたカーボンナノチューブの凝集体であり、内部や表層に薬物を貯留し徐放できる直径約100nmのナノ粒子である。CNHに抗がん剤のドキソルビシンを貯蔵させ徐放させる基盤技術の開発に取り組んだ。水溶性高分子ポリエチレングリコール(PEG)と抗がん剤ドキソルビシン(DXR)の複合体PEG-DXRで表面修飾することにより、水溶性ナノ粒子(PEG-DXR-CNH)に改変した。ヒト非小細胞肺癌細胞株NCI-H460のヌードマウス皮下移植モデルで、ドキソルビシンの高い腫瘍内滞留性による抗腫瘍効果が確認された。また、CNHが、がん転移先のセンチネルリンパ節組織に集積する傾向があることが明らかとなった。今後、リンパ節転移の診断と治療応用への展開が大いに期待出来る。
次に、ナノ粒子の光線力学療法への応用研究に取り組んだ。光感受性の亜鉛フタロシアニン(ZnPc)と親水性タンパク質を結合して、3者複合体ZnPc-CNH-BSAを作製することで、カーボンナノ粒子へ光治療用物質の内包に成功した。担がんマウスにナノ粒子複合体を投与し赤色レーザー光を照射したところ、腫瘍はほぼ消滅した。光照射でZnPcが活性酸素を発生してがん細胞を死滅させると同時に、ナノ粒子自体も光を吸収して温度上昇しがん細胞を死滅させるためと結論された。光線力学療法と温熱療法の二重の治療効果が期待出来る治療法開発につながる成果である。研究成果は、藤田保健衛生大学と産総研の研究チームとの共同研究として、各種メディアにプレスリリースした。

Report

(3 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (33 results)

All 2009 2008 2007 2006 Other

All Journal Article (19 results) (of which Peer Reviewed: 8 results) Presentation (10 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Water-dispersed single-wall carbon nanohorns as drug carders for local cancer chemotherapy.2008

    • Author(s)
      Murakami T, et al.
    • Journal Title

      Nanomedicine 3(4)

      Pages: 453-463

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fabrication of ZnPc/protein nanohorns for double photodyn amic and hyperthermic cancer phototherapy.2008

    • Author(s)
      Zhang M, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 105(39)

      Pages: 14773-14778

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of in vivo anti cancer effects of cisplatin by incorporation inside single-wall carbon nanohorns.2008

    • Author(s)
      Ajima K, et al.
    • Journal Title

      ACS Nano 2(10)

      Pages: 2057-2064

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent advances in inorganic nanoparticle-based drug delivery systems.2008

    • Author(s)
      Murakami T, Tsuchida K
    • Journal Title

      Mini Rev Med Chem 8

      Pages: 175-183

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Follistatin suppresses the production of experimental multiple-organ metastasis by small cell lung cancer cells in NK cell-depleted SCID mice.2008

    • Author(s)
      Ogino H, et. al.
    • Journal Title

      Clin Cancer Res 14

      Pages: 660-667

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer.2008

    • Author(s)
      Tsuchida K, et. al.
    • Journal Title

      Endocrine J 55

      Pages: 11-21

    • NAID

      10021264280

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent(S-1)with interferon-alpha.2007

    • Author(s)
      Miyake K, et. al.
    • Journal Title

      Cancer Chemother Pharmacol 59

      Pages: 113-126

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of preactivation by portal vein ligation on liver regeneration following massive hepatectomy in rats.2007

    • Author(s)
      Morine Y, et. al.
    • Journal Title

      Hepatogastroenterology 54

      Pages: 1216-1221

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha2007

    • Author(s)
      K.Miyake, K.Tsuchida, H.Sugino, S.Imura, Y.Morine, M.Fujii, M.Shimada
    • Journal Title

      Cancer Chemotherapy. Pharmacol. 59(1)

      Pages: 113-126

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Purification of recombinant activin A using the second follistatin domain of follistatin-related gene (FLRG)2006

    • Author(s)
      K.Y.Arai, K.Tsuchida, C.M.Li, G.Watanabe, H.Sugino, K.Taya, T.Nishiyama
    • Journal Title

      Protein Purification and Expression 49(1)

      Pages: 78-82

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transcriptional regulation of mouse mast cell protease-7 by TGF-beta2006

    • Author(s)
      M.Funaba, T.Ikeda, M.Murakami, K.Ogawa, Y Nishino, K.Tsuchida, H.Sugino, M.Abe
    • Journal Title

      Biochemi. Biophys. Acta 1759(3-4)

      Pages: 166-170

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Characterization of splicing variants of activin receptor-interacting protein 2 that augment activin signaling2006

    • Author(s)
      Z.H.Liu, K.Tsuchida, T Matsuzaki, Y.L.Bao, A Kurisaki, H.Sugino
    • Journal Title

      J.Endocrinology 189(2)

      Pages: 409-421

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Involvement of p38 MAP kinase and Smad3 in TGF-beta-mediated mast cell functions2006

    • Author(s)
      M.Funaba, T.Ikeda, M.Murakami, K.Ogawa, Y.Nishino, K.Tsuchida, H.Sugino, M.Abe
    • Journal Title

      Cell.Signal. 18

      Pages: 2154-2161

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 筋萎縮をきたす神経・筋難病の新しい治療法の開発2006

    • Author(s)
      土田邦博
    • Journal Title

      日本神経精神薬理学雑誌(Jpn.J.Neuropsychopharmacol.) 26

      Pages: 229-233

    • NAID

      10021190492

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of tocophenol-associated protein as an activin/TGF-beta inducible gene in mast cells2006

    • Author(s)
      M.Funaba, M.Murakami, T.Ikeda, K.Ogawa, K.Tsuchida, H.Sugino
    • Journal Title

      Biochemi.Biophys.Acta 1763(8)

      Pages: 900-906

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Requirement of Smad3 for mast cell growth2006

    • Author(s)
      M.Funaba, K.Nakaya, T.Ikeda, M.Murakami, K.Tsuchida, H.Sugino
    • Journal Title

      Cellular Immunology 240(1)

      Pages: 47-52

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ALK7 is a novel marker for adipocyte differentiation2006

    • Author(s)
      M.Kogame, S.Matsuo, M.Nakatani, A.Kurisaki, H.Nishitani, K.Tsuchida, H.Sugino
    • Journal Title

      J.Med.Invest. 53(3-4)

      Pages: 238-245

    • NAID

      130004465099

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitors for the TGF-beta superfamily and their clinical applications2006

    • Author(s)
      K.Tsuchida, Y.Sunada, S.Noji, T.Murakami, A.Uezumi, M.Nakatani
    • Journal Title

      Mini.Rev.Med.Chem. 6(11)

      Pages: 1255-1261

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition2006

    • Author(s)
      Y.Ohsawa, H.Hagiwara, M.Nakatani, A.Yasue, K.Moriyama, T.Murakami, K.Tsuchida, S.Noji, Y.Sunada
    • Journal Title

      J.Clin.Invest. 116(11)

      Pages: 2924-2934

    • Related Report
      2006 Annual Research Report
  • [Presentation] DDS応用を目指したリポ蛋白質の高機能化 ナノテクノロジーを用いた新しいドラッグ・デリバリー・システムの開発2008

    • Author(s)
      村上達也, 土田邦博
    • Organizer
      第24回日本DDS学会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] Preparation and functional analyses of water-dispersed carbon nanohorns for cancer chemotherapy.2008

    • Author(s)
      T. Murakami, H. Sawada, M. Yudasaka, S. Iijima, K. Tsuchida.
    • Organizer
      Controlled Release Society35th Annual Meeting& Exposition.
    • Place of Presentation
      New York, U.S.A.
    • Related Report
      2008 Annual Research Report
  • [Presentation] 蛋白質工学的手法を駆使した機能性リポ蛋白質の作製2008

    • Author(s)
      村上達也, ら
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] DDS application of single-wall Carbon nanohoms.2008

    • Author(s)
      Yudasaka M, et. al.
    • Organizer
      American Physical Society March Meeting
    • Place of Presentation
      New Orleans, Louisiana, USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] DDS application of single-wall Carbon nanohorns.2007

    • Author(s)
      Yudasaka M, et. al.
    • Organizer
      第四回日韓シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2007-10-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] 抗癌剤担持水溶性カーボンナノホーンの薬理評価2007

    • Author(s)
      村上達也, ら
    • Organizer
      第23回日本DDS学会
    • Place of Presentation
      熊本
    • Related Report
      2007 Annual Research Report
  • [Presentation] 葉酸ラベルによるカーボンナノホーンのヒト癌細胞への特異的取り込み2007

    • Author(s)
      宮脇仁, ら
    • Organizer
      第23回日本DDS学会
    • Place of Presentation
      熊本
    • Related Report
      2007 Annual Research Report
  • [Presentation] 癌細胞ターゲッティングを目指したカーボンナノホーンの葉酸ラベル2007

    • Author(s)
      宮脇仁, ら
    • Organizer
      日本化学会
    • Place of Presentation
      東京首都大学
    • Related Report
      2007 Annual Research Report
  • [Presentation] 局所投与用ドラッグキャリアとしてのカーボンナノホーン2007

    • Author(s)
      村上達也, ら
    • Organizer
      第29回日本バイオマテリアル学会
    • Place of Presentation
      大阪
    • Related Report
      2007 Annual Research Report
  • [Presentation] 抗癌活性を有するナノ粒子カーボンナノホーンのin vitroおよびin vivo機能評価2007

    • Author(s)
      村上達也, ら
    • Organizer
      日本分子生物学会日本生化学会合同大会(BMB2007)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Book] 機能性リポタンパク質「機能性DDSキャリアの製剤設計」(岡田弘晃監修)2009

    • Author(s)
      村上達也, 土田邦博
    • Total Pages
      321
    • Publisher
      シーェムシー出版
    • Related Report
      2008 Annual Research Report
  • [Book] Encyclopedia of Cancer2008

    • Author(s)
      Tsuchida K
    • Publisher
      Springer(印刷中)
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.fujita-hu.ac.jp/ICMS/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.fujita-hu.ac.jp/ICMS/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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