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Nano-sized MRI contrast agents for ultra-sensitive imaging of tumor microenvironment

Research Project

Project/Area Number 18K12079
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKyushu University

Principal Investigator

Kawano Takahito  九州大学, 先端医療オープンイノベーションセンター, 特任講師 (90526831)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsMRI / 造影剤 / タンパク質 / 癌 / ナノ材料 / 画像診断 / 膵癌 / ナノカプセル / DDS / タンパク質カプセル / 分子イメージング / 画像診断システム
Outline of Final Research Achievements

MRI (Magnetic Resonance Imaging) has the advantage of spatial resolution and non-invasiveness, but it has the disadvantage of sensitivity in detecting disease sites. In this study, we investigated to develop a new functional MRI nano-contrast agent that can improve the accuracy and sensitivity of MRI diagnosis, visualize the microenvironment of the tumor, and enable functional diagnosis of pathological conditions. Protein nanocapsules were used as the base of the MRI nanocontrast agent, and tumor-selective iRGD peptides were incorporated into the surface of the nanocapsules and gadolinium molecules were encapsulated inside. When the nanocapsules were administered to tumor-bearing mice , it was confirmed that the tumor could be detected using MRI. We also confirmed that the nanocapsules were almost free of cytotoxicity.

Academic Significance and Societal Importance of the Research Achievements

ナノカプセルは細胞毒性が低く、その体内動態は特に指向性もなく1時間程度で腎排出されることが分かっているが、今回、分子イメージング技術を用いてカプセル表面に腫瘍特異性iRGDペプチドを提示することで、MRIにより病変部位の検出が可能となった。このナノ造影剤を用いることによって、超早期画像診断の実現や、これまで組織レベルまで拡大進行した病変しか検出できなかった画像診断を、細胞から分子レベルの病変で見いだすMRIの機能診断への可能性を秘めていると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 2 results) Presentation (1 results) Book (1 results)

  • [Journal Article] Effect of Fetal Bovine Serum Concentration on Lysophosphatidylcholine-mediated Proliferation and Apoptosis of Human Aortic Smooth Muscle Cells2020

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

      Journal of Oleo Science

      Volume: 69 Issue: 3 Pages: 255-260

    • DOI

      10.5650/jos.ess19268

    • NAID

      130007804109

    • ISSN
      1345-8957, 1347-3352
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells2020

    • Author(s)
      Mizuta Yukie、Akahoshi Tomohiko、Guo Jie、Zhang Shuo、Narahara Sayoko、Kawano Takahito、Murata Masaharu、Tokuda Kentaro、Eto Masatoshi、Hashizume Makoto、Yamaura Ken
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 11 Issue: 1

    • DOI

      10.1186/s13287-020-02015-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design of substrates and inhibitors of G protein-coupled receptor kinase 2 (GRK2) based on its phosphorylation reaction2020

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

      Amino Acids

      Volume: 52 Issue: 6-7 Pages: 863-870

    • DOI

      10.1007/s00726-020-02864-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sodium thiosulfate prevents doxorubicin-induced DNA damage and apoptosis in cardiomyocytes in mice2020

    • Author(s)
      Mizuta Yukie、Tokuda Kentaro、Guo Jie、Zhang Shuo、Narahara Sayoko、Kawano Takahito、Murata Masaharu、Yamaura Ken、Hoka Sumio、Hashizume Makoto、Akahoshi Tomohiko
    • Journal Title

      Life Sciences

      Volume: 257 Pages: 118074-118074

    • DOI

      10.1016/j.lfs.2020.118074

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histidine-rich Glycoprotein alleviate Ischemia/Reperfusion Liver Injury in Mice with Nonalcoholic Steatohepatitis.2020

    • Author(s)
      Guo J, Akahoshi T, Mizuta Y, Murata M, Narahara S, Kawano T, Nagao Y, Zhang S, Tomikawa M, Kawanaka H, Hashizume M.
    • Journal Title

      Liver Transpl.

      Volume: Epub Issue: 6 Pages: 840-853

    • DOI

      10.1002/lt.25960

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A high-affinity peptide substrate for G protein-coupled receptor kinase 2 (GRK2)2019

    • Author(s)
      Daisuke Asai, Masaharu Murata, Riki Toita, Takahito Kawano, Hideki Nakashima, Jeong-Hun Kang
    • Journal Title

      Amino acids

      Volume: 51 Issue: 6 Pages: 973-976

    • DOI

      10.1007/s00726-019-02735-0

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppression of lysophosphatidylcholine-induced human aortic smooth muscle cell calcification by protein kinase A inhibition2019

    • Author(s)
      Riki Toita, Daisuke Asai, Kentaro Otani, Takahito Kawano, Masaharu Murata, Jeong-Hun Kang
    • Journal Title

      Lipids

      Volume: 54 Issue: 8 Pages: 465-470

    • DOI

      10.1002/lipd.12178

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Corrigendum to “Protein kinase A (PKA) inhibition reduces human aortic smooth muscle cell calcification stimulated by inflammatory response and inorganic phosphate” [Life Sci. 209(2018) 466?471]2019

    • Author(s)
      Toita Riki、Otani Kentaro、Kawano Takahito、Fujita Satoshi、Murata Masaharu、Kang Jeong-Hun
    • Journal Title

      Life Sciences

      Volume: 224 Pages: 138-138

    • DOI

      10.1016/j.lfs.2019.03.050

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ultrasensitive MRI detection of spontaneous pancreatic tumors with nanocage-based targeted contrast agent.2018

    • Author(s)
      Kawano T, Murata M, Kang JH, Piao JS, Narahara S, Hyodo F, Hamano N, Guo J, Oguri S, Ohuchida K, Hashizume M
    • Journal Title

      Biomaterials

      Volume: 152 Pages: 37-46

    • DOI

      10.1016/j.biomaterials.2017.10.029

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Protein kinase A (PKA) inhibition reduces human aortic smooth muscle cell calcification stimulated by inflammatory response and inorganic phosphate2018

    • Author(s)
      Riki Toita, Kentaro Otani, Takahito Kawano, Satoshi Fujita, Masaharu Murata, Jeong-Hun Kang
    • Journal Title

      Life Sciences

      Volume: 209 Pages: 466-471

    • DOI

      10.1016/j.lfs.2018.08.051

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ligand-Mediated Coating of Liposomes with Human Serum Albumin2018

    • Author(s)
      Sato Hikari、Nakhaei Elnaz、Kawano Takahito、Murata Masaharu、Kishimura Akihiro、Mori Takeshi、Katayama Yoshiki
    • Journal Title

      Langmuir

      Volume: 34 Issue: 6 Pages: 2324-2331

    • DOI

      10.1021/acs.langmuir.7b04024

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 河野 喬仁・楢原 佐由子・大内田 研宙・赤星朋比古・村田 正治2019

    • Author(s)
      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
    • Organizer
      第25回癌治療増感研究会
    • Related Report
      2019 Research-status Report
  • [Book] 医療に活かす生体医工学2020

    • Author(s)
      日本生体医工学会、平田 雅之、齋藤 充弘、紀ノ岡 正博、和田 成生、伊井 仁志、大谷 智仁、武石 直樹、橋爪 誠、大城 理、岡山 慶太、坂田 泰史、河野 喬仁、村田 正治、佐久間 一郎、篠原 一彦、江藤 正俊、小林 聡、牟田口 淳、今田 憲二郎、家入 里志、山田 耕嗣、大西 峻、山家 智之、不二門 尚、松村 泰志、野村 泰伸
    • Total Pages
      224
    • Publisher
      コロナ社
    • ISBN
      9784339072471
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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