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Protein Nanocages-Conjugated Magnetic Resonance Contrast Agents Displaying High Relaxivity and Tumor Selectivity.

Research Project

Project/Area Number 24300172
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionKyushu University

Principal Investigator

MURATA Masaharu  九州大学, 学内共同利用施設等, 准教授 (30304744)

Co-Investigator(Kenkyū-buntansha) 橋爪 誠  九州大学, 医学(系)研究科(研究院), 教授 (90198664)
濱野 展人  九州大学, 先端医療イノベーションセンター, 研究員 (80708397)
河野 喬仁  九州大学, 先端融合医療レドックスナビ研究拠点, 研究員 (90526831)
Co-Investigator(Renkei-kenkyūsha) HASHIZUME Makoto  九州大学, 大学院医学研究院, 教授 (90198664)
KAWANO Takahito  九州大学, 先端融合医療レドックスナビ研究拠点, 特任助教 (90526831)
HAMANO Nobuhito  九州大学, 先端医療イノベーションセンター研究拠点, 特任助教 (80708397)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords分子イメージング / ナノ材料 / MRI / 造影剤 / タンパク工学 / 癌
Outline of Final Research Achievements

In this study, small heat shock protein 16.5 (Hsp16.5)-based nanocages conjugated with gadolinium(III)-chelated MRI contrast agents were developed for the diagnosis of pancreatic cancer. Nanocages with one to four hydrophobic domains were designed to investigate whether template size influences relaxivity. MRI data showed that larger nanocages have higher T1 relaxivities than smaller nanocages as a result of 1) a reduction in molecular tumbling rates caused by an increase in nanocage size and 2) a robust cage structure resulting from the introduction of hydrophobic domains. The introduction of iRGD peptides that specifically target neuropilin-1 enabled the selective binding of nanocages to pancreatic cancer cells. Therefore, this iRGD- modified Hsp16.5 nanocage displays great potential as a highly specific and sensitive MRI contrast agent for the diagnosis of pancreatic cancer.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Invited: 1 results)

  • [Journal Article] Design and function of engineered protein nanocages as a drug delivery system for targeting pancreatic cancer cells via neuropilin-12015

    • Author(s)
      Masaharu Murata, Sayoko Narahara, Takahito Kawano, Nobuhito Hamano, Jing Shu Piao, Jeong-Hun Kang, Kenoki Ohuchida, Takashi Murakami, Makoto Hashizume
    • Journal Title

      Molecular Pharmaceutics

      Volume: in press Issue: 5 Pages: 1422-1430

    • DOI

      10.1021/mp5007129

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Peptide substrates for G protein-coupled receptor kinase 22014

    • Author(s)
      D. Asai, R. Toita, M. Murata, Y. Katayama, H. Nakashima, J.H. Kang
    • Journal Title

      FEBS Lett.

      Volume: Vol.588 Issue: 13 Pages: 2129-2132

    • DOI

      10.1016/j.febslet.2014.04.038

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and characterization of myristoylatedpreS1-conjugated nanocages for targeted cell delivery2014

    • Author(s)
      Murata M, Piao JS, Narahara S, Kawano T, Hamano N, Kang JH, Asai D, Ugawa R, Hashizume M,
    • Journal Title

      Protein Expressionand Purification

      Volume: 110 Pages: 52-56

    • DOI

      10.1016/j.pep.2014.12.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic Delivery of Protein Nanocages Bearing CTT Peptides for Enhanced Imaging of MMP-2 Expression in Metastatic Tumor Models Authors2014

    • Author(s)
      Kawano T, Murata M, Piao J, Narahara S, Hamano N, Kang J, Hashizume M
    • Journal Title

      Int J Mol Sci

      Volume: 16(1) Issue: 1 Pages: 148-158

    • DOI

      10.3390/ijms16010148

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver cell-specific peptides derived from the PreS1 domain of human hepatitis B virus2014

    • Author(s)
      J.H. Kang, R. Toita, D. Asai, T. Yamaoka, M. Murata
    • Journal Title

      J Virol Methods

      Volume: Vol.201 Pages: 20-23

    • DOI

      10.1016/j.jviromet.2014.02.013

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mass Spectrometry-based Metabolic Profiling of Gemcitabine-sensitive and Gemcitabine-resistant Pancreatic Cancer Cells2014

    • Author(s)
      Fujimura Y, Ikenaga N, Ohuchida K, Setoyama D, Irie M, Miura D, Wariishi H, Murata M, Mizumoto K, Hashizume M, Tanaka M
    • Journal Title

      Pancreas

      Volume: 43(2) Issue: 2 Pages: 311-318

    • DOI

      10.1097/mpa.0000000000000092

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biological Evaluation of Protein Nanocapsules Containing Doxorubicin2013

    • Author(s)
      Riki Toita
    • Journal Title

      International Journal of Nanomedicine

      Volume: 8 Pages: 1989-1999

    • DOI

      10.2147/ijn.s40239

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A nanocarrier based on a genetically engineered protein cage to deliver doxorubicin to human hepatocellular carcinoma cells2013

    • Author(s)
      Riki Toita, Masaharu Murata, Kana Abe, Sayoko Narahara, Jing Shu Piao, Jeong-Hun Kang and Makoto Hashizume
    • Journal Title

      Chemical Communications

      Volume: 49 Issue: 67 Pages: 7442-7444

    • DOI

      10.1039/c3cc44508a

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification2012

    • Author(s)
      Akira Tsuchiya, et al
    • Journal Title

      Journal of Biomedical Materials Research Part A

      Volume: 100 Issue: 5 Pages: 1136-1141

    • DOI

      10.1002/jbm.a.34049

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Human Hepatocellular Carcinoma Cell-Targeted Protein Cages2012

    • Author(s)
      Riki Toita, Masaharu Murata, Shigekazu Tabata, Kana Abe, Sayoko Narahara, Jing Shu Piao, Jeong-Hun Kang,and Makoto Hashizume
    • Journal Title

      Bioconjugate Chemistry

      Volume: 23 Issue: 7 Pages: 1494-1501

    • DOI

      10.1021/bc300015f

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages2012

    • Author(s)
      Masaharu Murata, Sayoko Narahara, Kaori Umezaki, Riki Toita, Shigekazu Tabata, Jing Shu Piao, Kana Abe, Jeong-Hun Kang, Kenoki Oouchida, Lin Cui, Makoto Hashizume
    • Journal Title

      International Journal of Nanomedicine

      Volume: 7 Pages: 4353-4362

    • DOI

      10.2147/ijn.s31365

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] TARGETD DRUG DELIVERY USING GENETICALLY ENGINEERED PROTEIN NANOCAGE FOR PANCREATIC CANCER2014

    • Author(s)
      Masaharu Murata, Sayoko Narahara, Jing Shu Piao, Takahito Kawano, Nobuhito Hamano, Kenoki Ohuchida, Makoto Hashizume
    • Organizer
      2nd International Translational Nanomedicine Conference
    • Place of Presentation
      Northeastern University
    • Year and Date
      2014-07-25 – 2014-07-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] タンパク質ナノキャリアの機能化による構造制御と薬物放出2013

    • Author(s)
      村田 正治、楢原 佐由子、朴 晶淑、河野 喬仁、濱野 展人、大内田 研宙、橋爪 誠
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都テルサ
    • Related Report
      2013 Annual Research Report
  • [Presentation] タンパク質ナノカプセルを用いた高感度MRIプローブの開発2013

    • Author(s)
      河野 喬仁、村田 正治、朴 晶淑、楢原 佐由子、濱野 展人、大内田 研宙、橋爪 誠
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都テルサ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵癌標的化タンパク質ナノカプセルの分子設計と機能評価2013

    • Author(s)
      楢原 佐由子、村田 正治、朴 晶淑、河野 喬仁、濱野 展人、大内田 研宙、橋爪 誠
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都テルサ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Liver cell specific targeting by PreS1 Peptide-carrying nanocages2013

    • Author(s)
      M.Murata,S.Narahara,R.Toita,J-S.Piao,M.Hashizume
    • Organizer
      40st Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Hawaii Convention Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] プロテインナノカプセルをプラットフォームとする分子イメージング試薬の開発2013

    • Author(s)
      村田正治
    • Organizer
      日本分析化学会第62年会
    • Place of Presentation
      近畿大学東大阪キャンパス
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] プロテインナノケージの機能化とターゲティングデリバリー2012

    • Author(s)
      村田正治、楢原佐由子、他6名
    • Organizer
      日本バイオマテリアル学会シンポジウム2012
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2012-11-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] タンパク質ナノカプセルの機能化とドラッグデリバリーへの応用2012

    • Author(s)
      村田正治、楢原佐由子、他6名
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学高等教育推進機構
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] ガドリニウム錯体内包タンパク質ナノカプセルを用いたMRI造影剤の開発2012

    • Author(s)
      河野喬仁、村田正治、他4名
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学高等教育推進機構
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] 膵癌標的化タンパク質ナノカプセルの設計と機能評価2012

    • Author(s)
      楢原佐由子、村田正治、他6名
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学高等教育推進機構
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] 先端医療におけるナノ診断とナノ治療2012

    • Author(s)
      村田正治
    • Organizer
      第49回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場(招待講演)
    • Year and Date
      2012-06-30
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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