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Evaluation on EPR effect and active control of EPR effect for achieving efficient tumor accumulation of nanocarrier delivery system

Research Project

Project/Area Number 21689002
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

ISHIDA Tatsuhiro  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (50325271)

Co-Investigator(Renkei-kenkyūsha) KIWADA Hiroshi  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (50120184)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2010: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2009: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
KeywordsDDS / ナノキャリア / 腫瘍 / EPR効果 / がん治療 / 抗がん剤 / リポソーム / 腫瘍内微小環境 / メトロノミック・ケモセラピー / 抗がく剤
Research Abstract

Chemotherapy delivered in nanocarriers has been developed to improve the clinical treatment of solid tumors by achieving high accumulation of chemotherapeutic agents in tumor tissues but limited accumulation in healthy organs via due to the so-called" enhanced permeability and retention(EPR) effect". We showed that low dose metronomic chemotherapy given the damage in endothelial cells of growing tumor vasculature and tumor cells, increased tumor accumulation of nanocarriers as a result of vascular normalization and enlargement of intratumoral space in solid tumors. This strategy may be breakthrough in anti-cancer chemotherapy with nanocarrier-based anticancer drugs against intractable tumors which have lower vascular density and permeability.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2012 2011 2010 2009 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (23 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Combination therapy with metronomic S-1 dosing and oxaliplatin-containing PEG-coated cationic liposomes in a murine colorectal tumor model : Synergy or antagonism?2012

    • Author(s)
      Abu Lila, A. S., Okada, T., Doi, Y., Ichihara, M., Ishida, T., Kiwada, H.
    • Journal Title

      Int. J. Pharm.

      Volume: 426 Pages: 263-270

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Improved intratumoral delivery of PEG-coated siRNA-lipoplexes by combination with metronomic S-1 dosing in a murine solid tumor model2012

    • Author(s)
      Tagami, T., Abu Lila, A. S., Matsunaga, M., Moriyoshi, N., Nakamura, H., Nakamura, K., Suzuki, T., Doi, Y., Ishida, T., Kiwada, H.
    • Journal Title

      Drug Deliv. Transl. Res.

      Volume: 2 Pages: 77-86

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy with metronomic S-1 dosing and oxaliplatin-containing PEG-coated cationic liposomes in a murine colorectal tumor model : Synergy or antagonism?2012

    • Author(s)
      Abu Lila, A.S.
    • Journal Title

      Int.J.Pharm.

      Volume: 426 Pages: 263-270

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved intratumoral delivery of PEG-coated siRNA-lipoplexes by combination with metronomic S-1 dosing in a murine solid tumor model2012

    • Author(s)
      Tagami, T.
    • Journal Title

      Drug Deliv.Transl.Res.

      Volume: 2 Pages: 77-86

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] i-angiogenic therapy via cationic liposome-mediated systemic siRNA delive2012

    • Author(s)
      Tagami, T
    • Journal Title

      Int.J.Pharm.

      Volume: 422 Pages: 280-289

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A double-modulation strategy in cancer treatment with a chemotherapeutic agent and siRNA2011

    • Author(s)
      Nakamura, K, Abu Lila A., Matsunaga, M., Doi, Y., Ishida, T., Kiwada, H.
    • Journal Title

      Mol. Ther.

      Volume: 19 Pages: 2040-2047

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A double-modulation strategy in cancer treatment with a chemotherapeutic agent and siRNA2011

    • Author(s)
      Nakamura, K
    • Journal Title

      Mor.Ther.

      Volume: 19 Pages: 2040-2047

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Argonaute2 is a potential target for siRNA-based cancer therapy for HT1080 human fibrosarcoma2011

    • Author(s)
      Tagami, T.
    • Journal Title

      Drug Deliv.Transl.Res.

      Volume: 1 Pages: 277-288

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy of metronomic S-1 dosing with oxaliplatin-containing PEG-coated liposome improves antitumor activity in a murine colorectal tumor model2010

    • Author(s)
      Doi Y., Okada T., Matsumoto H., Ichihara M., Ishida T., Kiwada, H.
    • Journal Title

      Cancer Sci.

      Volume: 101 Pages: 2470-2475

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sequential administration with oxaliplatin-containing PEG-coated cationic liposomes promotes a significant delivery of subsequent dose into murine solid tumor2010

    • Author(s)
      Abu Lila, A., Doi, Y., Nakamura, K., Ishida, T., Kiwada, H.
    • Journal Title

      J. Control. Release

      Volume: 142 Pages: 167-173

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeting anticancer drugs to tumor vasculature using cationic liposomes2010

    • Author(s)
      Abu Lila, A., Ishida, T., Kiwada, H.
    • Journal Title

      Pharm. Res.

      Volume: 27 Pages: 1171-1183

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy of metronomic S-1 dosing with oxaliplatin-containing PEG-coated liposome improves antitumor activity in a murine colorectal tumor model.2010

    • Author(s)
      Doi Y.
    • Journal Title

      Cancer Sci.

      Volume: 101 Pages: 2470-2475

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Co-administration of tacrolimus suppresses pharmacokinetic modulation of multiple subcutaneously administrated human interferon-alpha in beagle dogs.2010

    • Author(s)
      Yamazaki, H.
    • Journal Title

      Drug Metab.Pharmacokinet.

      Volume: 25 Pages: 149-154

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential administration with oxaliplatin-containing PEG-coated cationic liposomes promotes a significant delivery of subsequent dose into murine solid tumor.2010

    • Author(s)
      Abu Lila, A.
    • Journal Title

      J.Control.Release

      Volume: 142 Pages: 167-173

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential administration with oxaliplatin-containing PEG-coated cationic 1 iposomes promotes a significant delivery of subsequent dose into murine solid tumor.2010

    • Author(s)
      Abu Lila, A.
    • Journal Title

      J.Control. Release 142

      Pages: 167-173

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting anticancer drugs to tumor vasculature using cationic liposomes.2010

    • Author(s)
      Abu Lila, A.
    • Journal Title

      Pharm.Res. (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxaliplatin encapsulated in PEG-coated cationic liposomes induces significant tumor growth suppression via a dual-targeting approach in a murine solid tumor model2009

    • Author(s)
      Abu Lila, A., Kizuki, S., Doi, Y., Suzuki, T., Ishida, T., Kiwada, H.
    • Journal Title

      J. Control. Release

      Volume: 137 Pages: 8-14

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic antitumor activity of metronomic dosing of cyclophosphamide in combination with doxorubicin-containing PEGylated liposomes in a murine solid tumor model2009

    • Author(s)
      Ishida, T., Shiraga, E., Kiwada, H.
    • Journal Title

      J. Control. Release

      Volume: 134 Pages: 194-200

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oxaliplatin targeting to angiogenic vessels by PEGylated cationic liposomes suppresses the angiogenesis in a dorsal air sac mouse model2009

    • Author(s)
      Abu-Lila, A, Suzuki, T., Doi, Y., Ishida, T., Kiwada, H.
    • Journal Title

      J. Control. Release

      Volume: 134 Pages: 18-25

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recent advances in tumor vasculature targeting using liposomal drug delivery systems2009

    • Author(s)
      Abu Lila, A., Ishida, T., Kiwada, H.
    • Journal Title

      Expert Opin. Drug Deliv.

      Volume: 6 Pages: 1297-1309

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic antitumor activity of metronomic dosing of cyclophosphamide in combination with doxorubicin-containing PEGylated liposomes in a murine solid tumor model.2009

    • Author(s)
      Ishida, T.
    • Journal Title

      J.Control. Release 134

      Pages: 194-200

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] S-1とオキサリプラチン封入PEG修飾リポソームの併用療法におけるリポソームの体内動態の変化に関する研究2012

    • Author(s)
      中村浩之
    • Organizer
      日本薬学会第126年会
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 腫瘍内微小環境の能動的制御に基づくsiRNAデリバリー技術の開発とがん治療への展開2012

    • Author(s)
      石田竜弘
    • Organizer
      日本薬学会第126年会
    • Place of Presentation
      北海道大学(北海道)(招待講演)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Development of new cancer treatment strategy that combines PEG-coated siRNA-lipoplex with metronomic S-1 dosing2011

    • Author(s)
      Moriyoshi, N.
    • Organizer
      International Liposome Society 2011 meeting
    • Place of Presentation
      University of London, London
    • Year and Date
      2011-12-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] フッ化ピリミジン系経口抗癌剤(S-1)がPEG修飾カチオニックリポソームの腫瘍移行性に与える影響2011

    • Author(s)
      岡田知子
    • Organizer
      第20回DDSカンファランス
    • Place of Presentation
      グランシップ(静岡)
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tegaful製剤S-1とsiRNA含有liposomeの併用による新規がん治療法の開発2011

    • Author(s)
      森吉直人
    • 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
      大阪大学(大阪)
    • Year and Date
      2011-09-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] 腫瘍内微小環境変化を利用した核酸デリバリー戦略2011

    • Author(s)
      石田竜弘
    • Organizer
      遺伝子・デリバリー研究会第11回夏期セミナー
    • Place of Presentation
      三翠園ホテル(高知)(招待講演)
    • Year and Date
      2011-08-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] PEG修飾リポソーム投与マウス脾臓中の抗PEG IgM分泌担当細胞の探索2011

    • Author(s)
      市原理子
    • Organizer
      第27回日本DDS学会学術集会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2011-06-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 抗がん剤封入PEG修飾リポソームにおけるABC現象(第2報):サルにおける検討2011

    • Author(s)
      鈴木卓也
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2011-05-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] Improvement of tumor-targeting therapy with nanocarrier system by changing the tumor microenviroment2011

    • Author(s)
      Ishida, T., Kiwada, H.
    • Organizer
      2011 RCAA International Symposium Endogenous Ligands Modulating Anticancer Agents
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-02-11
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] A novel double modulation strategy in cancer treatment with chemothera peutic agent and siRNA : S-1 improves siRNA accumulation and then Bcl-2 knockdown by the siRNA increases chemosensitivity of 5-FU.2011

    • Author(s)
      Ishida, T.
    • Organizer
      NANO IN CANCER : LINKING CHEMISTRY, BIOLOGY, AND CLINICAL APPLICATIONS IN VIVO
    • Place of Presentation
      Miami, USA
    • Year and Date
      2011-01-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腫瘍内微小環境変化を利用したsiRNAデリバリーシステムの開発2010

    • Author(s)
      石田竜弘、際田弘志
    • Organizer
      第32回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      富山
    • Year and Date
      2010-11-29
    • Related Report
      2011 Final Research Report
  • [Presentation] 腫瘍内微小環境変化を利用したsiRNAデリバリーシステムの開発2010

    • Author(s)
      石田竜弘
    • Organizer
      第32回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      富山市
    • Year and Date
      2010-11-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Metronomic oral S-1, a fluoropyrimidine anticancer agent, dosing affects tumor accumulation of PEG-coated liposome.2010

    • Author(s)
      Okada, T.
    • Organizer
      International Liposome Research Days & Lipids, Liposomes & Membrane Biophysics
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-08-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腫瘍へのsiRNAデリバリーシステムの開発~効果と安全性の観点から~2010

    • Author(s)
      石田竜弘
    • Organizer
      第47回薬剤学懇談会研究討論会
    • Place of Presentation
      高山
    • Year and Date
      2010-06-24
    • Related Report
      2011 Final Research Report
  • [Presentation] 腫瘍へのsiRNAデリバリーシステムの開発~効果と安全性の観点から~2010

    • Author(s)
      石田竜弘
    • Organizer
      第47回薬剤学懇談会研究討論会
    • Place of Presentation
      高山市
    • Year and Date
      2010-06-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 生体内動態検討を基盤としたリポソームDDSの開発2010

    • Author(s)
      石田竜弘
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪市
    • Year and Date
      2010-06-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] ナノキャリアに対するEPR効果に寄与する腫瘍内微小環境変化に関する研究:S-1の低用量頻回投与(metronomic chemotherapy)から得られた知見2010

    • Author(s)
      土井祐輔
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山市
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] がん細胞種が及ぼす抗がん剤封入リボソームの腫瘍移行性とその治療効果への影響2010

    • Author(s)
      松本春菜
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山市
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] フッ化ピリミジン系経口抗癌剤とOxaliplatin封入PEG修飾カチオニックリポソーム併用による抗腫瘍効果の検討2009

    • Author(s)
      岡田知子
    • Organizer
      第48回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Place of Presentation
      徳島市
    • Year and Date
      2009-11-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] S-1のmetronomic chemotherapyがもたらすナノキャリア腫瘍集積性向上に関わる腫瘍内微小環境変化2009

    • Author(s)
      土井祐輔
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] ナノキャリアに対するEPR効果に寄与する腫瘍内微小環境変化に関する検討.S-1の低用量頻回投与(metronomlc chemothera)から得られた知見2009

    • Author(s)
      土井祐輔
    • Organizer
      第18回DDSカンファレンス
    • Place of Presentation
      静岡市
    • Year and Date
      2009-09-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Argonaute2標的siRNAリポプレックスを用いたがん治療戦略、学術シンポジウム4 RNAi医薬の展望. From Bench to Bedside-2009

    • Author(s)
      石田竜弘、浅井知浩、奥直人、際田弘志
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Year and Date
      2009-05-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Improvement of tumor-targeting therapy with nanocarriers by changing the tumor microenvironment2009

    • Author(s)
      Ishida, T., Kiwada, H.
    • Organizer
      2009 International Symposium of the Intelligent Drug Delivery System.
    • Place of Presentation
      Korea
    • Year and Date
      2009-04-30
    • Related Report
      2011 Final Research Report
  • [Book] Cationic liposomes and tumour vasculature targeting : a therapeutic approach that has potential for solid tumours2011

    • Author(s)
      Abu Lila A. S., Ishida T., Kiwada, H.
    • Publisher
      i-Smithers-Creative Publishing Solutions
    • Related Report
      2011 Final Research Report
  • [Book] Breaking the barriers to tumor-targeting via nanocarrier-based drug delivery to the tumor microenvironment2010

    • Author(s)
      Doi, Y., Ishida, T., Kiwada, H.
    • Publisher
      Nova Science Publishers
    • Related Report
      2011 Final Research Report
  • [Book] A book chaper in Cancer Targeted Therapy ; Breaking the barriers to tumor-targeting via nanocarrier-based drug delivery to the tumor microenvironment.2010

    • Author(s)
      Doi, Y.
    • Publisher
      Nova Science Publishers(In Press)
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.tokushima-u.ac.jp/ph/faculty/labo/ykz/

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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