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Evaluation of antitumor effect of tumor-associated macrophage-targeting liposomes

Research Project

Project/Area Number 23790203
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionHoshi University

Principal Investigator

HATTORI Yoshiyuki  星薬科大学, 薬学部, 准教授 (90350222)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords葉酸受容体 / リポソーム / マクロファージ / ゾレドロン酸 / がん治療 / 抗がん剤 / 抗がん薬
Research Abstract

We investigated the possibility of whether depletion of tumor-associated macrophages (TAMs) by zoledronic acid (ZOL) entrapped in folate-linked liposome (FL-ZOL) could inhibit tumor angiogenesis and consequently tumor growth. FL-ZOL showed high cytotoxicity for FR-positive KB and murine macrophage RAW264.7 cells, but not for FR-negative Colon 26 cells, suggested that FL-ZOL was selectively taken up via FR-mediated endocytosis. However, injections of FL-ZOL did not induce antitumor activities for KB and Colon 26 tumor-bearing mice, and had a lethal effect by high toxicity. From these findings, the severe in vivo toxicity of liposomal ZOL limited its utility for in vivo TAM targeting, although FL-ZOL could selectively induce in vitro cytotoxicity via FR.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (29 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (14 results) Remarks (3 results)

  • [Journal Article] In vivo siRNA delivery system for targeting to the liver by poly-L-glutamic acid-coated lipoplex2014

    • Author(s)
      Y. Hattori, A. Nakamura, S. Arai, M. Nishigaki, H. Ohkura, K. Kawano, Y. Maitani and E. Yonemochi
    • Journal Title

      Results in Pharma Sciences

      Volume: 4 Pages: 1-7

    • DOI

      10.1016/j.rinphs.2014.01.001

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transdermal delivery of small interfering RNA with elastic cationic liposomes in mice2013

    • Author(s)
      Y. Hattori, M. Date, S. Arai, K. Kawano, E. Yonemochi, Y. Maitani
    • Journal Title

      Journal of Pharmaceutics

      Volume: 2013 Pages: 149695-149695

    • DOI

      10.1155/2013/149695

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anionic polymer-coated lipoplex for safe gene delivery into tumor by systemic injection2013

    • Author(s)
      Y. Hattori, H. Yamasaku, Y. Maitani
    • Journal Title

      J. Drug Target

      Volume: 21(7) Issue: 7 Pages: 639-647

    • DOI

      10.3109/1061186x.2013.789035

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy with gefitinib and doxorubicin inhibits tumor growth in transgenic mice with adrenal neuroblastoma2013

    • Author(s)
      K. Kawano, Y. Hattori, H. Iwakura, T. Akamizu and Y. Maitani
    • Journal Title

      Cancer Medicine

      Volume: 2(3) Issue: 3 Pages: 286-295

    • DOI

      10.1002/cam4.76

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced Plasmid DNA Transfer into Tumor Cells by Nanoparticle Composed of Cholesteryl Triamine and Diamine2013

    • Author(s)
      Y. Hattori, T. Nakamura, H, Ohno, N. Fujii, Y. Maitani
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 36 Issue: 5 Pages: 856-860

    • DOI

      10.1248/bpb.b12-01062

    • NAID

      130003361415

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] siRNA delivery for tumor by lipid-based nanoparticle composed with hydroxyethylated cholesteryl triamine2013

    • Author(s)
      Y. Hattori, T. Nakamura, H, Ohno, N. Fujii, Y. Maitani
    • Journal Title

      Int. J. Pharm.

      Volume: 443 Issue: 1-2 Pages: 221-229

    • DOI

      10.1016/j.ijpharm.2012.12.017

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Collagenase-1 injection improved tumor distribution and gene expression of cationic lipoplex2012

    • Author(s)
      M. Kato, Y. Hattori, M. Kubo and Y. Maitani
    • Journal Title

      Int. J. Pharm

      Volume: 423(2) Issue: 2 Pages: 428-434

    • DOI

      10.1016/j.ijpharm.2011.12.015

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early entry and deformation of macropinosomes correlates with high efficiency of decaarginine-PEG-lipid-mediated gene delivery2012

    • Author(s)
      Kobayashi, S.
    • Journal Title

      J.Gene Med.

      Volume: 14 Issue: 4 Pages: 262-271

    • DOI

      10.1002/jgm.2615

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adrenal tumor volume in a genetically engineered mouse model of neuroblastoma determined by magnetic resonance imaging2012

    • Author(s)
      K. Kawano, Y. Hattori, H. Iwakura, T. Akamizu, Y. Maitani
    • Journal Title

      Exp. Ther. Med.

      Volume: 4 Issue: 1 Pages: 61-64

    • DOI

      10.3892/etm.2012.564

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of transcription factor Ets-1 in the expression of the α3 integrin subunit gene.2012

    • Author(s)
      Kamoshida G, Matsuda A, Katabami K, Kato T, Mizuno H, Sekine W, Oku T, Itoh S, Tsuiji M, Hattori Y, Maitani Y, Tsuji T.
    • Journal Title

      FEBS J.

      Volume: 279(24) Issue: 24 Pages: 4535-46

    • DOI

      10.1111/febs.12040

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antitumor Effect of Liposomal Histone Deacetylase Inhibitor-Lipid Conjugates in Vitro2011

    • Author(s)
      Y.Hattori, Y.Nagaoka, Shinichi Uesato, 他4名
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 59 Issue: 11 Pages: 1386-1392

    • DOI

      10.1248/cpb.59.1386

    • NAID

      130001274814

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell line-dependent internalization pathways determine DNA transfection efficiency of decaarginine-PEG-lipid2011

    • Author(s)
      T. Izumisawa, Y. Hattori, M. Date, K. Toma, Y. Maitani
    • Journal Title

      The International Journal of Pharmaceutics

      Volume: 404 Issue: 1-2 Pages: 264-270

    • DOI

      10.1016/j.ijpharm.2010.11.017

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 腫瘍関連マクロファージを標的としたゾレドロン酸封入葉酸修飾リポソーム製剤による抗腫瘍効果の評価2014

    • Author(s)
      山下潤,坂井田知里,川野久美,服部喜之,米持悦生
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍関連マクロファージを標的としたゾレドロン酸封入葉酸修飾リポソーム製剤による抗腫瘍効果の評価2014

    • Author(s)
      山下潤,坂井田知里,川野久美,服部喜之,米持悦生
    • Organizer
      日本薬学会 第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規正電荷コレステロール誘導体を用いて調製した脂質ナノ粒子製剤によるがん細胞へのsiRNA送達2013

    • Author(s)
      服部喜之,中村司,大野浩章,藤井信孝,米谷芳枝
    • Organizer
      第13回遺伝子・デリバリー研究会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2013-05-11
    • Related Report
      2013 Final Research Report
  • [Presentation] 固形がんにおける葉酸受容体の発現と腫瘍関連マクロファージ標的ゾレドロン酸封入葉酸修飾リポソーム製剤の開発2013

    • Author(s)
      山下潤,坂井田知里,服部喜之,米谷芳枝
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 安全性の高いsiRNA導入用負電荷ポリマー被覆リポプレックス製剤の開発2013

    • Author(s)
      中村文子,服部喜之,西垣磨優,大倉博之,山作晴香,米谷芳枝
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 固形がんにおける葉酸受容体の発現と腫瘍関連マクロファージ標的ゾレドロン酸封入葉酸修飾リポソーム製剤の開発2013

    • Author(s)
      山下 潤、坂井田 知里、服部 喜之、米谷 芳枝
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 副腎腫瘍発症遺伝子改変マウスにおけるドキソルビシン封入リポソームの治療効果2013

    • Author(s)
      川野 久美、服部 喜之、岩倉 浩、赤水 尚史、米谷 芳枝
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 第8回つくばがん遺伝子治療研究会2012

    • Author(s)
      服部喜之
    • Organizer
      がん遺伝子治療のための非ウイルスベクターの開発
    • Place of Presentation
      東京
    • Year and Date
      2012-07-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 脂質ナノ粒子製剤を用いたがんへの遺伝子送達2012

    • Author(s)
      服部喜之
    • Organizer
      第34回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 甲状腺乳頭癌における葉酸受容体発現,金本巨哲2012

    • Author(s)
      服部喜之,上田依利子,曽根正勝,三浦晶子,八十田明宏,荒井宏司,米谷芳枝,中尾一和
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] がん遺伝子導入用負電荷ポリマー被覆リポプレックス製剤の開発2011

    • Author(s)
      山作晴香,服部喜之,米谷芳枝
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] コラゲナーゼ処理した担がんマウスにおけるリポプレックスの腫瘍集積性及び遺伝子発現2011

    • Author(s)
      服部喜之,加藤真子,久保愛美,米谷芳枝
    • Organizer
      アンチセンス・遺伝子・デリバリー シンポジウム 2011
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] siRNA送達用肝臓標的ナノ粒子製剤の開発

    • Author(s)
      新井翔平,服部喜之,米持悦生
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規正電荷コレステロール誘導体を用いて調製した脂質ナノ粒子製剤による がん細胞へのsiRNA送達

    • Author(s)
      服部喜之,中村司,大野浩章,藤井信孝,米谷芳枝
    • Organizer
      第13回 遺伝子・デリバリー研究会シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://polaris.hoshi.ac.jp/kyoshitsu/souzai/index.htm

    • Related Report
      2013 Final Research Report
  • [Remarks] 星薬科大学 創剤構築研究室

    • URL

      http://polaris.hoshi.ac.jp/kyoshitsu/souzai/index.htm

    • Related Report
      2013 Annual Research Report
  • [Remarks] 星薬科大学 創剤構築研究室

    • URL

      http://polaris.hoshi.ac.jp/kyoshitsu/souzai/index1.html

    • Related Report
      2012 Research-status Report

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

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