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Targeting ability of systemically administered drug-loaded polymeric micelles against lymph node metastasis

Research Project

Project/Area Number 23700526
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biological material science
Research InstitutionThe University of Tokyo

Principal Investigator

CABRAL Horacio  東京大学, 大学院・工学系研究科, 講師 (10533911)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsドラッグデリバリー / リンパ節転移 / 高分子型ミセル / 高分子ミセル / オキサリプラチン
Research Abstract

Tumor spread to distant organs and lymph nodes is the most threatening aspect of cancer. Current therapeutic strategies against lymphatic metastases show low efficiency and high morbidity. Here, the targeting ability of systemically administered drug-loaded polymeric micelles against lymph node metastasis was evaluated for developing an efficacious therapy against lymphatic metastasis. Thus, a model of early lymph node metastasis was developed by using bioluminescent murine melanoma B16-F10-Luc cells, injected in the forepaw of mice, while the micelles were prepared by the complex formation between the carboxylic moieties of PEG-b-poly(glutamic acid) copolymer and (1,2-diaminocyclohexane) platinum(II), the parent complex of oxaliplatin. Micelles accumulated in metastatic lymph nodes regardless of the presence of primary tumor, achieving significant antitumor effect. Moreover, the size of the micelle affected their targeting ability against lymph node metastasis, as micelles with 30-nm diameter were more efficient than micelles with 70-nm diameter. This size effect was also observed against the lymph node metastasis of a bioluminescent orthotopic model of human scirrhous gastric cancer. The ability of 30-nm micelles to target lymph node metastases may provide a novel approach for early diagnosis and efficient therapy.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (42 results)

All 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (36 results) Remarks (1 results)

  • [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
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bioactivepolymeric metallosomesself-assembled through blockcopolymer-metal complexation.2012

    • Author(s)
      K. Osada, H. Cabral, Y. Mochida, S. -ELee, K. Nagata, T. Matsuura, M.Yamamoto, Y. Anraku, A. Kishimura, N.Nishiyama, K. Kataoka
    • Journal Title

      J. Am.Chem. Soc.

      Volume: 134(32) Issue: 32 Pages: 13172-13175

    • DOI

      10.1021/ja304615y

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis2012

    • Author(s)
      M. Rafi
    • Journal Title

      J. Control. Release

      Volume: 159 Issue: 2 Pages: 189-196

    • DOI

      10.1016/j.jconrel.2012.01.038

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of theDynamics of Drug Delivery Systems (DDS)Using Intravital Real-Time Confocal LaserScanning Microscopy2012

    • Author(s)
      Takahiro Nomoto、Yu Matsumoto、KazukoToh、R. James Christie、Kanjiro Miyata、Makoto Oba、Horacio Cabral、Mami Murakami、Shigeto Fukushima、Nobuhiro Nishiyama、Kazunori Kataoka
    • Journal Title

      Yakugaku Zasshi

      Volume: 132巻 Pages: 1347-1354

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the Dynamics of Drug Delivery Systems (DDS) Using Intravital Real-Time Confocal Laser Scanning Microscopy2012

    • Author(s)
      Takahiro Nomoto, Horacio Cabral, 他9名
    • Journal Title

      Yakugaku Zasshi

      Volume: 132 Pages: 1347-1354

    • NAID

      130002489530

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Intracellular delivery of proteasome inhibitor MG132 by using polymeric micelles for effective cancer therapy2013

    • Author(s)
      Sabina Quader, Horacio Cabral, Yuki Mochida, Takehiko Ishii, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      2nd International Conference on Biomaterials Science in Tsukuba ICBS2013
    • Place of Presentation
      つくば国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] PEGylated Polyanion Hybrid Calcium Phosphate Micellar MRI Probe for In Vivo Noninvasive Solid Tumor Diagnosis2013

    • Author(s)
      Peng Mi, Daisuke Kokuyo, Michiaki Kumagai, Horacio Cabral, Ichio Aoki, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      16th International Symposium on RECENTADVANCES IN DRUG DELIVERY SYSTEMS
    • Place of Presentation
      Salt Lake City (USA)
    • Related Report
      2012 Final Research Report
  • [Presentation] Secondary Structure of PEG-b-Poly(Glutamic Acid) Copolymer Determines the Drug Delivery Efficiency of Cisplatin-Loaded Polymeric Micelles2013

    • Author(s)
      Yuki Mochida, Francesco Albertini, Horacio Cabral, Yutaka Miura, KensukeOsada, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      16th International Symposium on RECENT ADVANCES IN DRUG DELIVERY SYSTEMS
    • Place of Presentation
      Salt Lake City (USA)
    • Related Report
      2012 Final Research Report
  • [Presentation] Intracellular delivery of proteasome inhibitor MG132 by using polymeric micelles for effective cancer therapy2013

    • Author(s)
      Sabina Quader, Horacio Cabral, 他4名
    • Organizer
      2nd Internat. Conf. on Biomaterials Sci. in Tsukuba -ICBS2013-
    • Place of Presentation
      つくば国際会議場(茨城県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] PEGylated polyanion hybrid calcium phosphate micellar MRI probe for in vivo noninvasive solid tumor diagnosis2013

    • Author(s)
      Peng Mi, Horacio Cabral 他5名
    • Organizer
      16th International Symposium on RECENT ADVANCES IN DRUG DELIVERY SYSTEMS
    • Place of Presentation
      Salt Lake City (USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Secondary structure of PEG-b-poly(glutamic acid) copolymer determines the drug delivery efficiency of cisplatin-loaded polymeric micelles2013

    • Author(s)
      Yuki Mochida, Horacio Cabral 他5名
    • Organizer
      16th International Symposium on RECENT ADVANCES IN DRUG DELIVERY SYSTEMS
    • Place of Presentation
      Salt Lake City (USA)
    • Related Report
      2012 Annual Research Report
  • [Presentation] がんのリンパ行性転移に対する高分子ミセル型DDSのターゲティング能に関する研究2012

    • Author(s)
      牧野惇、Horacio Cabral、松本有、三浦裕、狩野光伸、西山伸宏、片岡一則
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] 悪性脳腫瘍を標的としたリガンド介在型ドラッグデリバリーシステムの開発2012

    • Author(s)
      三浦裕、Horacio Cabral、西山伸宏、片岡一則
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Size-mediated accumulation of sub-100 nm polymeric micelles in poorly permeable tumors2012

    • Author(s)
      Horacio Cabral, Yu Matsumoto, Mitsunobu R. Kano, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Targeting of early inflammatory metastatic sites by using drug-loaded polymeric micelles2012

    • Author(s)
      Hailiang Wu, Horacio Cabral, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Developing pH-responsive Polymer Micelles for the intracellular delivery of Proteasome inhibitor M132 for effective cancer therapy2012

    • Author(s)
      Sabina Quader, Horacio Cabral, Takehiko Ishii, Yutaka Miura, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      The 9th International PolymerConference (IPC 2012)
    • Place of Presentation
      神戸コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Structure and enhanced pharmacokinetics of antitumor platinum-loaded micelles regulated by secondary structure in their core2012

    • Author(s)
      Yuki Mochida, Francesco Albertini, Horacio Cabral, Yutaka Miura, Kensuke Osada, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      The 9th International Polymer Conference (IPC2012)
    • Place of Presentation
      神戸コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Calcium Phosphate Hybrid Micelles Incorporating Gd-DTPA with Enhance Relaxivity for Magnetic Resonance Imaging2012

    • Author(s)
      Peng Mi, H or a ci o Ca b r al , Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      The 9th International Polymer Conference (IPC2012)
    • Place of Presentation
      神戸コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Preparation of antibody introduced micelle consist of well defined end-functiolized P(ethylene oxidel)-b-poly(amino aicd)2012

    • Author(s)
      Jooyeon Ahn, Yutaka Miura, Hirokuni Uchida, H or a ci o C abr a l , Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      The 9th International Polymer Conference (IPC2012)
    • Place of Presentation
      神戸コンベンションセ ンター
    • Related Report
      2012 Final Research Report
  • [Presentation] 疎水性薬剤を内包したポリイオンコンプレックス型ベシクルPICsomeの開発2012

    • Author(s)
      笹野将人、安楽泰孝、岸村顕広、Horacio Cabral、西山伸宏、片岡一則
    • Organizer
      第61回高分子討論会
    • Place of Presentation
      名古屋工業大学
    • Related Report
      2012 Final Research Report
  • [Presentation] αヘリックス構造形成に基づくPEG-ポリグルタミン酸ブロック共重合体/制がん剤ダハプラチン内包高分子ミセルの機能向上2012

    • Author(s)
      持田祐希、Francesco Albertini, Horacio Cabral,三浦裕,長田健介,西山伸宏,片岡一則
    • Organizer
      第61回高分子討論会
    • Place of Presentation
      名古屋工業大学
    • Related Report
      2012 Final Research Report
  • [Presentation] 白金錯体制がん剤内包ミセルのコア高次構造が形態及び薬剤機能に及ぼす影響2012

    • Author(s)
      持田祐希、Francesco Albertini、Horacio Cabral、三浦裕、長田健介、西山伸宏、片岡一則
    • Organizer
      第61回高分子年次大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Formation and sustained-dissociation of antitumor platinum-loaded micelles regulated by secondary structure in their core2012

    • Author(s)
      Yuki Mochida, Francesco Albertini, Horacio Cabral, Yutaka Miura, Kensuke Osada, Nobuhiro Nishiyama, KazunoriKataoka
    • Organizer
      9th World Biomaterials Congress
    • Place of Presentation
      Chengdu (China)
    • Related Report
      2012 Final Research Report
  • [Presentation] Ichio Aoki, Kazunori Kataoka, Gd-DTPA loaded polymeric micelle with high relaxivity for in vivo cancer diagnosis2012

    • Author(s)
      Peng Mi, Horacio Cabral , Sachiko Kaida, Daisuke Kokuryo, Nobuhiro Nishiyama
    • Organizer
      9th World Biomaterials Congress
    • Place of Presentation
      Chengdu (China)
    • Related Report
      2012 Final Research Report
  • [Presentation] Preparation and Characterization of pH-responsive Polymeric Micelles Incorporating the Proteasome Inhibitor MG132 for Efficient Cancer Therapy2012

    • Author(s)
      Sabina Quader, Horacio Cabral, Takehiko Ishii, Yutaka Miura, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      The 39th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Centre des congres de Quebec, Quebec City (Canada)
    • Related Report
      2012 Final Research Report
  • [Presentation] Polymeric Micelles Can Treat Lymph Node Metastasis After Intravenous Injection2012

    • Author(s)
      Horacio Cabral, Jun Makino, TakahiroNomoto, Mitsunobu R. Kano, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      NanoBio Seattle 2012 (The Fourth International NanoBio Conference)
    • Place of Presentation
      Seattle (USA)
    • Related Report
      2012 Final Research Report
  • [Presentation] がんのリンパ行性転移に対する高分子ミセル型DDSの ターゲティング能に関する研究2012

    • Author(s)
      牧野 惇, Horacio Cabral 他3名
    • Organizer
      第28回 日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 悪性脳腫瘍を標的としたリガンド介在型ドラッグデリバリーシステムの開発2012

    • Author(s)
      三浦裕、Horacio Cabral, 他2名
    • Organizer
      第28回 日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Size-mediated accumulation of sub-100 nm polymeric micelles in poorly permeable tumors2012

    • Author(s)
      Horacio Cabral, 他4名
    • Organizer
      第28回 日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Targeting of early inflammatory metastatic sites by using drug-loaded polymeric micelles2012

    • Author(s)
      Huailiang Wu, Horacio Cabral, 他4名
    • Organizer
      第28回 日本DDS学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Developing pH-responsive Polymer Micelles for the intracellular delivery of Proteasome inhibitor M132 for effective cancer therapy2012

    • Author(s)
      Sabina Quader;Horacio Cabral; 他4名
    • Organizer
      The 9th International Polymer Conference(IPC2012)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Structure and enhanced pharmacokinetics of antitumor platinum-loaded micelles regulated by secondary structure in their core2012

    • Author(s)
      Yuki Mochida;Horacio Cabral; 他5名
    • Organizer
      The 9th International Polymer Conference(IPC2012)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Calcium Phosphate Hybrid Micelles Incorporating Gd-DTPA with Enhance Relaxivity for Magnetic Resonance Imaging2012

    • Author(s)
      Peng Mi;Horacio Cabral; 他2名
    • Organizer
      The 9th International Polymer Conference(IPC2012)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Preparation of antibody introduced micelle consist of well defined end-functionalized poly(ethylene oxide)- b-poly(amino acid)2012

    • Author(s)
      Jooyeon Ahn;Horacio Cabral; 他4名
    • Organizer
      The 9th International Polymer Conference(IPC2012)
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of a polyion complex polymersome (PICsome) containing surfactant micelles with hydrophobic drugs in aqueous interior2012

    • Author(s)
      Masato Sasano,Horacio Cabral 他4名
    • Organizer
      The 61st Symposium on Macromolecules
    • Place of Presentation
      名古屋工業大学(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Improved function of antitumor DACHPt-loaded polymeric micelles based on α -helical structure of PEG-b -poly(glutamic acid)2012

    • Author(s)
      Yuki Mochida, Horacio Cabral 他5名
    • Organizer
      The 61st Symposium on Macromolecules
    • Place of Presentation
      名古屋工業大学(愛知県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 白金錯体制がん剤内包ミセルのコア高次構造が 形態及び薬剤機能に及ぼす影響2012

    • Author(s)
      持田 祐希, Horacio Cabral 他5名
    • Organizer
      The 61st SPSJ Annual meeting
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Formation and sustained-dissociation of antitumor platinum-loaded micelles regulated by secondary structure of poly(amino acids) in their core2012

    • Author(s)
      Yuki Mochida, Horacio Cabral 他5名
    • Organizer
      9th World Biomaterials Congress
    • Place of Presentation
      Chengdu (China)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Gd-DTPA loaded polymeric micelle with high relaxivity for in vivo cancer diagnosis2012

    • Author(s)
      Mi Peng, Horacio Cabral 他5名
    • Organizer
      9th World Biomaterials Congress
    • Place of Presentation
      Chengdu (China)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Preparation and Characterisation of pH-responsive Polymeric Micelles Incorporating the Proteasome Inhibitor MG132 for Efficient Cancer Therapy2012

    • Author(s)
      Sabina Quader、Horacio Cabral 他5名
    • Organizer
      2012 CRS Annual Meeting
    • Place of Presentation
      Centre des congrès de Québec Québec City (Canada)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Polymeric micelles inhibit the growth of lymph node metastasis after intravenous injection2012

    • Author(s)
      Horacio Cabral 他5名
    • Organizer
      NanoBioSeattle
    • Place of Presentation
      Seattle (USA)
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.bmw.t.u-tokyo.ac.jp/

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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