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Biodegradable nano-cages for controlled drug release

Research Project

Project/Area Number 15K12544
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKyushu University

Principal Investigator

Murata Masaharu  九州大学, 先端医療イノベーションセンター, 特任教授 (30304744)

Co-Investigator(Kenkyū-buntansha) 橋爪 誠  九州大学, 医学研究院, 教授 (90198664)
河野 喬仁  九州大学, 先端医療イノベーションセンター, 特任助教 (90526831)
濱野 展人  九州大学, 先端医療イノベーションセンター, 特任助教 (80708397)
Co-Investigator(Renkei-kenkyūsha) HASHIZUME MAKOTO  九州大学, 大学院医学研究院, 教授 (90198664)
TOMIKAWA MORIMASA  九州大学, 病院 先端医工学診療部, 准教授 (60325454)
TAKAHITO KAWANO  九州大学, 先端医療イノベーションセンター, 助教 (90526831)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsナノ材料 / DDS / がん / タンパク質工学 / ナノメディスン
Outline of Final Research Achievements

We describe the development of neuropilin 1-binding peptide (iRGD)-nanocages that specifically targethuman pancreatic cancer cells in which an iRGD is joined to the surface of naturally occurring heat shock protein (HSP) cages. Using a genetic engineering approach, the iRGD domain was joined to the C-terminal region of the HSP cage using flexible linker moieties. The characteristics of the interdomain linkages between the nanocage and the iRGD domain play an important role in the specificity and affinity of the iRGD-nanocages for their target cells. Furthermore, a moderately hydrophobic anticancer drug, OSU03012, was successfully incorporated into the L30-iRGD nanocage by heating the mixture. The OSU03012-loaded L30-iRGD-nanocage induced cell death of pancreatic cancer cells by activating the caspase cascade more effectively than the same concentrations of free OSU03012. The iRGD-nanocages show great potential as a novel nanocarrier for pancreatic cancer-targeted drug delivery.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2017 2016 2015 2014

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 7 results,  Acknowledgement Compliant: 6 results) Presentation (5 results) (of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Autophagy is required for activation of pancreatic sstellate cells, associated with pancreatic cancer progression and promotes growth of pancreatic tumors in mice.2017

    • Author(s)
      Endo S, Nakata K, Ohuchida K, Takesue S, Nakayama H, Abe T, Koikawa K, Okumura T, Sada M, Horioka K, Zheng B, Mizuuchi Y, Iwamoto C, Murata M, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
    • Journal Title

      Gastroenterology

      Volume: 印刷中 Issue: 6 Pages: 1492-1506

    • DOI

      10.1053/j.gastro.2017.01.010

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In vivo redox metabolic imaging of mitochondria assesses disease progression in non-alcoholic steatohepatitis2017

    • Author(s)
      Nakata R, Hyodo F, Murata M, Eto H, Nakaji T, Kawano T, Narahara S, Yasukawa K, Akahoshi T, Tomikawa M, Hashizume M
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 17170-17170

    • DOI

      10.1038/s41598-017-17447-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased hepatic inflammation in a normal-weight mouse after long-term high-fat diet feeding2017

    • Author(s)
      Riki TOITA, Takahito KAWANO, Satoshi FUJITA, Masaharu MURATA, Jeong-Hun KANG
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 31 Issue: 1 Pages: 43-47

    • DOI

      10.1293/tox.2017-0038

    • NAID

      130006318210

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of amino acid residues surrounding the phosphorylation site in peptide substrates of G protein-coupled receptor kinase 2 (GRK2)2016

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

      Amino Acids

      Volume: 48 Issue: 12 Pages: 2875-2880

    • DOI

      10.1007/s00726-016-2345-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Noninvasive mapping of the redox status of dimethylnitrosamine-induced hepatic fibrosis using in vivo dynamic nuclear polarization-magnetic resonance imaging2016

    • Author(s)
      Kawano T, Murata M, Hyodo F, Eto H, Kosem N, Nakata R, Hamano N, Piao JS, Narahara S, Akahoshi T, Hashizume M
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1 Pages: 32604-32604

    • DOI

      10.1038/srep32604

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Förster Resonance Energy Transfer-Based Self-Assembled Nanoprobe for Rapid and Sensitive Detection of Postoperative Pancreatic Fistula2016

    • Author(s)
      Nobuhito Hamano, Masaharu Murata, Takahito Kawano, Jing Shu Piao, Sayoko Narahara, Ryosuke Nakata, Tomohiko Akahoshi, Tetsuo Ikeda, and Makoto Hashizume
    • Journal Title

      ACS Applied Materials & Interfaces

      Volume: 8 Issue: 8 Pages: 5144-5123

    • DOI

      10.1021/acsami.5b11902

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Basic FGF-treated adipose tissue-derived mesenchymel stem cell infusion ameliorate liver cirrhosis via paracrine HGF2015

    • Author(s)
      Tang W, Aakahoshi T, Piao J, Narahara S, Murata M, Kawano T, Hamano N, Ikeda T, Hashizume M
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 20 Issue: 6 Pages: 1065-1074

    • DOI

      10.1111/jgh.12893

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Monitoring of phosphorylated peptides by radioactive assay and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry2015

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

      Amino Acids

      Volume: 47 Issue: 11 Pages: 2377-2383

    • DOI

      10.1007/s00726-015-2025-y

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [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
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Forster Resonance Energy Transfer-Based Self-Assembled Nanoprobe for Rapid and Sensitive Detection of Postoperative Pancreatic Fistula2017

    • Author(s)
      Jie Guo, M. Murata, S. Narahara, J.-S. Piao, T. Kawano, N. Hamano, R. Nakata, M. Hashizume
    • Organizer
      Biomaterials International
    • Place of Presentation
      福岡
    • Year and Date
      2017-08-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Engineered protein nanocages for drug delivery in pancreatic cancer2016

    • Author(s)
      M. Murata, S. Narahara, J.-S. Piao, T. Kawano, N. Hamano, R. Nakata, M. Hashizume
    • Organizer
      17th Tetrahedron symposium
    • Place of Presentation
      スペイン
    • Year and Date
      2016-06-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Liver cell specific targeting by myristoylated preS1-conjugated nanocages for drug delivery Abstract Body2015

    • Author(s)
      Masaharu Murata, Jing Shu Piao, Sayoko Narahara, Takahito Kawano, Nobuhito Hamano, Makoto Hashizume
    • Organizer
      Pacifichem2015
    • Place of Presentation
      ホノルルコンベンションセンター
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neuropilin-1を分子標的とした膵がん標的化ナノカプセルのDDS応用2015

    • Author(s)
      楢原 佐由子、村田 正治、朴 晶淑、河野 喬仁、濱野展人、橋爪 誠
    • Organizer
      日本DDS学会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 分解型ナノカプセルによるsiRNAデリバリーシステムの開発2015

    • Author(s)
      朴 晶淑、村田 正治、楢原 佐由子、河野 喬仁、濱野展人、橋爪 誠
    • Organizer
      日本DDS学会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 膵液検出用蛍光プローブ、膵液検出方法及び膵液検出用キット2015

    • Inventor(s)
      村田正治、橋爪 誠、濱野展人、池田哲夫、赤星朋比古
    • Industrial Property Rights Holder
      国立大学法人 九州大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-202419
    • Filing Date
      2015-10-13
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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