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Development of smart MRI contrast agents based on polymeric micelles to detect tumor microenvironment

Research Project

Project/Area Number 25670010
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionTokyo Institute of Technology

Principal Investigator

NISHIYAMA Nobuhiro  東京工業大学, 資源化学研究所, 教授 (10372385)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords高分子ミセル / がん / イメージング / MRI / 低酸素領域 / 微小転移 / 診断
Outline of Final Research Achievements

To improve the accuracy of MR imaging, the development of tumor-specific MRI contrast agents have been strongly demanded. In this study, we have developed polymeric micelles composed of calcium phosphate core, which can exhibit dissolution responding to acidic pH environment in the tumor tissue and incorporated Mn2+ ions, an MRI contrast agent, into the micelles. Polymeric micelles could release Mn2+ ions selectively under the acidic conditions mimicking the tumor microenvironments, and the released Mn2+ ions showed T1 shortening through the interaction with proteins. The in vivo experiments revealed that Mn2+ ions-loaded micelles displayed remarkably enhanced tumor-specific contrast enhancement compared with clinically used MRI contrast agents. Also, the Mn2+ ions-loaded micelles have been demonstrated to be useful for MR imaging of tumor hypoxia and small metastases in the liver.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2015 2014 2013 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (11 results) (of which Invited: 11 results) Book (5 results) Remarks (2 results)

  • [Journal Article] Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer2015

    • Author(s)
      J. -Y. Ahn, Y. Miura, N. Yamada, T. Chida, X. Liu, A. Kim, R. Sato, R. Tsumura, Y. Koga, M. Yasunaga, N. Nishiyama, Y. Matsumura, H. Cabral, K. Kataoka
    • Journal Title

      Biomaterials

      Volume: 39 Pages: 23-30

    • DOI

      10.1016/j.biomaterials.2014.10.069

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Light-induced cytosolic activation of reduction-sensitive camptothecin-loaded polymeric micelles for spatiotemporally controlled in vivo chemotherapy2014

    • Author(s)
      H.-C. Yen, H. Cabral, P. Mi, K. Toh, Y. Matsumoto, X. Liu, H. Koori, A. Kim, K. Miyazaki, Y. Miura, N. Nishiyama, K. Kataoka
    • Journal Title

      ACS Nano

      Volume: 8 Issue: 11 Pages: 11591-11602

    • DOI

      10.1021/nn504836s

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation2014

    • Author(s)
      H. Wu, H. Cabral, K. Toh, P. Mi, Y.-C. Chen, Y. Matsumoto, N. Yamada, X. Liu, H. Kinoh, Y. Miura, M. R. Kano, H. Nishihara, N. Nishiyama, K. Kataoka
    • Journal Title

      J. Control. Release

      Volume: 189 Pages: 1-10

    • DOI

      10.1016/j.jconrel.2014.06.018

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bundled assembly of helical nanostructures in polymeric micelles loaded with platinum drugs enhancing therapeutic efficiency against pancreatic tumor2014

    • Author(s)
      Y. Mochida, H. Cabral, Y. Miura, F. Albertini, S. Fukushima, K. Osada, N. Nishiyama, K. Kataoka
    • Journal Title

      ACS Nano

      Volume: 8 Issue: 7 Pages: 6724-6738

    • DOI

      10.1021/nn500498t

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer2014

    • Author(s)
      T. Nomoto, S. Fukushima, M. Kumagai, K. Machitani, Arnida, Y. Matsumoto, M. Oba, K. Miyata, K. Osada, N. Nishiyama, K. Kataoka
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 3545-3545

    • DOI

      10.1038/ncomms4545

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors2014

    • Author(s)
      P. Mi, D. Kokuryo, H. Cabral, M. Kumagai, T. Nomoto, I. Aoki, Y. Terada, A. Kishimura, N. Nishiyama, K. Kataoka
    • Journal Title

      J. Control. Release

      Volume: 174 Pages: 63-71

    • DOI

      10.1016/j.jconrel.2013.10.038

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] siRNA delivery from triblock copolymer micelles with spatially-ordered compartmants of PEG shell, siRNA-loaded intermediate layer, and hydrophobic core2014

    • Author(s)
      Hyun Jin Kim, Kanjiro Miyata, Takahiro Nomoto, Meng Zheng, Ahram Kim, Xueying Liu, Horacio Cabral, R. James Christie, Nobuhiro Nishiyama, Kazunori Kataoka
    • Journal Title

      Biomaterials

      Volume: 35 Issue: 15 Pages: 4548-4556

    • DOI

      10.1016/j.biomaterials.2014.02.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multicompartment micelles with adjustable poly (ethylene glycol) shell for efficient in vivo photodynamic therapy2014

    • Author(s)
      C. V. Synatschke, N. Nishiyama, et al.
    • Journal Title

      ACS Nano

      Volume: (in press)(印刷中)(掲載確定) Issue: 2 Pages: 1161-1172

    • DOI

      10.1021/nn4028294

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic mice by PEGylated calcium phosphate hybrid micelles2014

    • Author(s)
      F. Pittella, N. Nishiyama, et al.
    • Journal Title

      J. Control. Release

      Volume: 178 Pages: 18-24

    • DOI

      10.1016/j.jconrel.2014.01.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elucidating the molecular mechanism for the intracellular trafficking and fate of block copolymer micelles and their components2014

    • Author(s)
      K. -S. Kato, N. Nishiyama, et al.
    • Journal Title

      Biomaterials

      Volume: 35 Issue: 5 Pages: 1347-1358

    • DOI

      10.1016/j.biomaterials.2013.11.027

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors2014

    • Author(s)
      P. Mi, N. Nishiyama, et al.
    • Journal Title

      J. Control. Release

      Volume: 136 Issue: 1 Pages: 157-163

    • DOI

      10.1021/ja406992w

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier2013

    • Author(s)
      Y. Miura, N. Nishiyama, et al.
    • Journal Title

      ACS Nano

      Volume: 7 Issue: 10 Pages: 8583

    • DOI

      10.1021/nn402662d

    • URL

      https://localhost/en/publications/3467d27d-2dd8-4c3f-989a-c9fd3270117c

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors.2013

    • Author(s)
      S. Deshayes, N. Nishiyama, et al.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 135 Issue: 41 Pages: 15501-15507

    • DOI

      10.1021/ja406406h

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis2013

    • Author(s)
      H. Cabral, N. Nishiyama, et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 110 Issue: 28 Pages: 11397-11402

    • DOI

      10.1073/pnas.1301348110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] SPIO-PlCsome : Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes)2013

    • Author(s)
      D. Kokuryo, N. Nishiyama, et al.
    • Journal Title

      J. Control. Release

      Volume: 169 Issue: 3 Pages: 220-227

    • DOI

      10.1016/j.jconrel.2013.03.016

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging2013

    • Author(s)
      P. Mi, H. Cabrala, D. Kokuryo, M. Rafi, Y. Terada, I. Aoki, T. Saga, T. Ishii, N. Nishiyama, K. Kataoka
    • Journal Title

      Biomaterials

      Volume: 34 Issue: 2 Pages: 492-500

    • DOI

      10.1016/j.biomaterials.2012.09.030

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 生体イメージングを活用したナノDDS設計2014

    • Author(s)
      西山伸宏
    • Organizer
      疾患克服を目指したケミカルバイオフォトニクス技術 第87回日本生化学会大会
    • Place of Presentation
      京都国際会館, 京都市, 京都府
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 高分子ミセル型ナノ医薬品の研究開発2014

    • Author(s)
      西山伸宏
    • Organizer
      新製剤技術とエンジニアリングを考える会 第12回技術講演会
    • Place of Presentation
      京都国際会館, 京都市, 京都府
    • Year and Date
      2014-07-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Biological functionalities of polymeric micelle systems for targeting cancer2014

    • Author(s)
      N. Nishiyama
    • Organizer
      The European Summit for Clinical Nanomedicine 2014 (6th CLINAM 2014)
    • Place of Presentation
      Congress Center Basel, Basel, Switzerland
    • Year and Date
      2014-06-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 高分子ナノテクノロジーを基盤とするナノ医薬品の開発2014

    • Author(s)
      西山伸宏
    • Organizer
      第10回つくばがん遺伝子治療研究会
    • Place of Presentation
      ステーションコンファレンス東京, 東京
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] がんの診断・治療のための高分子ミセル型DDSの開発2014

    • Author(s)
      西山伸宏
    • Organizer
      本病院薬剤師会東北ブロック第4回学術大会
    • Place of Presentation
      仙台国際センター, 仙台市, 宮城県
    • Year and Date
      2014-05-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Development of supramolecular nanocarriers for cancer diagnosis and therapy2014

    • Author(s)
      N. Nishiyama
    • Organizer
      Emerging Biomaterials 2014
    • Place of Presentation
      KAIST Institute, Seoul, Korea
    • Year and Date
      2014-05-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] がんの診断・治療のための高分子ミセル型DDSの開発2013

    • Author(s)
      西山 伸宏
    • Organizer
      製剤機械技術学会 第23回大会
    • Place of Presentation
      ニッショーホール (東京都、港区)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] がんの革新的診断・治療のためのスマート機能型高分子ミセルの開発2013

    • Author(s)
      西山 伸宏
    • Organizer
      BioJapan 2013
    • Place of Presentation
      パシフィコ横浜 (神奈川県、横浜市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 高分子ナノテクノロジーによるがんの診断・治療システムの創製2013

    • Author(s)
      西山 伸宏
    • Organizer
      東京工業大学 バイオマテリアルシンポジウム
    • Place of Presentation
      東京工業大学すずかけホール (神奈川県、横浜市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Development of polymeric micellar nanocarriers for cancer diagnosis and therapy2013

    • Author(s)
      N. Nishiyama
    • Organizer
      The 4th Asian Biomaterials Congress
    • Place of Presentation
      The Hong Kong University of Science and Technology (Hong Kong, China)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Development of supramolecular nanocarriers for cancer diagnosis and therapy2013

    • Author(s)
      N. Nishiyama
    • Organizer
      2013 International Advanced Drug Delivery Symposium
    • Place of Presentation
      ITRI (Taiwan)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] ナノメディシン-副作用のない理想的な医薬品の実現に向けて2015

    • Author(s)
      西山伸宏
    • Publisher
      現代化学 東京化学同人
    • Related Report
      2014 Annual Research Report
  • [Book] ナノメディシンによる革新的医薬品の実現に向けて2014

    • Author(s)
      西山伸宏
    • Publisher
      BIO Clinica 北隆館/ニューサイエンス社
    • Related Report
      2014 Annual Research Report
  • [Book] 高分子ナノテクノロジーを利用したナノメディシンの開発2014

    • Author(s)
      西山伸宏
    • Publisher
      最新医学 最新医学社
    • Related Report
      2014 Annual Research Report
  • [Book] 高分子ナノパーティクルを用いたDDSの展開2014

    • Author(s)
      西山伸宏
    • Publisher
      医薬ジャーナル 医薬ジャーナル社
    • Related Report
      2014 Annual Research Report
  • [Book] 標的指向性DDS開発の新展開 メディカルサイエンスダイジェスト(Vol.40 No.2)「DDS技術の進歩と医療応用」2014

    • Author(s)
      西山 伸宏
    • Total Pages
      106
    • Publisher
      ニューサイエンス社
    • Related Report
      2013 Research-status Report
  • [Remarks] 東京工業大学 資源化学研究所 西山研究室ホームページ

    • URL

      http://www.res.titech.ac.jp

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京工業大学 資源化学研究所 西山研究室ホームページ

    • URL

      http://www.bmw.res.titech.ac.jp

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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