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Development of a novel type worm-like DDS penetrable into tumor tissue

Research Project

Project/Area Number 23390014
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

KOGURE Kentaro  京都薬科大学, 薬学部, 教授 (70262540)

Co-Investigator(Kenkyū-buntansha) TSUCHIY Hiroyuki  前京都薬科大学, 薬学部, 講師 (00403402)
HAMA Susumu  京都薬科大学, 薬学部, 講師 (60438041)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
KeywordsナノDDS / 癌細胞間隙 / 癌微小環境 / 癌治療 / siRNA
Research Abstract

In this study, we attempted to develop a novel type worm-like DDS for overcoming drawbacks of conventional nanoDDS for anticancer therapy, such as, antigenicity of PEG, low cell affinity and low permeability into tumor tissue. As the results, we successfully developed charge-invertible liposomes, which can response to tumor microenvironment, and the capabilities of endosomal escape and cellular internalization and tumor accumulation comparable to PEG-liposomes were confirmed. Moreover, the worm-like nanostructures, which can penetrate into narrow space, were developed, and significantly high permeability into spheroids was achieved by improvement of physicochemical property of wick structure, modification with hyaluronidase and functional peptides. Then, integration of those functional liposomes, and evaluation of in vivo functionality was started.

Report

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

    (43 results)

All 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (31 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Journal Article] Development of a novel nanoparticle by dual modification with the pluripotential cell-penetrating peptide PepFect6 for cellular uptake, endosomal escape, and decondensation of an siRNA core complex2013

    • Author(s)
      Mitsueda A, Shimatani Y, Ito M, Ohgita T, Yamada A, Hama S, Gräslund A, Lindberg S, Langel U, Harashima H, Nakase I, Futaki S, Kogure K
    • Journal Title

      Biopolymers

      Volume: Vol.100 Issue: 6 Pages: 698-704

    • DOI

      10.1002/bip.22310

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effects of topical application of a poorly soluble antioxidant astaxanthin liposomal formulation on ultraviolet-induced skin damage2012

    • Author(s)
      Hama S, Takahashi K, Inai Y, Shiota K, Sakamoto R, Yamada A, Tsuchiya H, Kanamura K, Yamashita E, Kogure K
    • Journal Title

      J Pharm Sci

      Volume: Vol.101 Issue: 8 Pages: 2909-2916

    • DOI

      10.1002/jps.23216

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a Novel Drug Delivery System consisting of an Antitumor Agent Tocopheryl Succinate2012

    • Author(s)
      Hama S, Utsumi S, Fukuda Y, Nakayama K, Okamura Y, Tsuchiya H, Fukuzawa K, Harashima H, Kogure K
    • Journal Title

      Journal of Control release

      Volume: 161(3) Issue: 3 Pages: 843-851

    • DOI

      10.1016/j.jconrel.2012.05.031

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage2012

    • Author(s)
      Kigasawa K, Miyashita M, Kajimoto K, Kanamura K, Harashima H, Kogure K
    • Journal Title

      Biol. Pharm. Bull

      Volume: Vol.35 Pages: 781-785

    • NAID

      130001872240

    • Related Report
      2013 Final Research Report
  • [Journal Article] A touch-and-go lipid wrapping technique in microfluidic channels for rapid fabrication of multifunctional envelope-type gene delivery nanodevices2011

    • Author(s)
      Kitazoe K, Wang J, Kaji N, Okamoto Y, Tokeshi M, Kogure K, Harashima H, Baba Y
    • Journal Title

      Lab Chip

      Volume: 11 Issue: 19 Pages: 3256-3262

    • DOI

      10.1039/c1lc20392d

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] invasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis2011

    • Author(s)
      Kajimoto K, Yamamoto M, Watanabe M, Kigasawa K, Kanamura K, Harashima H, Kogure K
    • Journal Title

      Int. J. Pharm

      Volume: Vol.403 Issue: 1-2 Pages: 57-65

    • DOI

      10.1016/j.ijpharm.2010.10.021

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage

    • Author(s)
      Kigasawa K, Miyashita M, Kajimoto K, Kanamura K, Harashima H, Kogure K
    • Journal Title

      Biol.Pharm.Bull.

      Volume: (印刷中)(印刷中につき未定)

    • NAID

      130001872240

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 柔軟な構造を有する組織浸透性siRNA キャリアーの開発2013

    • Author(s)
      小暮健太朗, 鄭 賢卿, 宇野晃平, 島谷悠里, 濵 進
    • Organizer
      第23回アンチセンスシンポジウム
    • Place of Presentation
      徳島
    • Related Report
      2013 Final Research Report
  • [Presentation] Efficient cytoplasmic delivery of siRNA by tumoral pH sensitive nanoparticles via membrane fusion under tumor microenvironment2013

    • Author(s)
      Itakura S. Hama S. Nakai M. Nakayama K. Morimoto S. Tsuchiya H. Kogure K
    • Organizer
      40th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Hawaii, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] A flexible nano carrier for siRNA delivery into tumor2013

    • Author(s)
      Kogure K. Shimatani Y. Uno K. Chon H.K. Hama S
    • Organizer
      40th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Hawaii, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍低pH応答性ナノ粒子の効率的な細胞質送達メカニズムの解析2013

    • Author(s)
      濱 進, 板倉祥子, 中井麻友美, 中山佳代子, 森本智士, 小暮健太朗
    • Organizer
      第29回日本DDS 学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍集積性向上のための腫瘍微弱低pH応答性リポソームの改良と機能性評価2013

    • Author(s)
      森本智士, 濱 進, 板倉祥子, 中井麻友美, 中山佳代子, 土谷博之, 小暮健太朗
    • Organizer
      第29回日本DDS 学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍の微弱低pH に応答して細胞内取り込みが促進されるSAPS ペプチド修飾ナノ粒子の機能性評価2013

    • Author(s)
      中山佳代子, 濱 進, 板倉祥子, 中井麻友美, 森本智士, 大石利一, 土谷博之, 小暮健太朗
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍内部への浸透を目指した新規siRNA キャリアーの開発2013

    • Author(s)
      宇野晃平, 鄭 賢卿, 濱 進, 小暮健太朗
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍内部への浸透を目指した新規siRNAキャリアーの開発2013

    • Author(s)
      宇野晃平
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      愛知県名古屋市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腫瘍の微弱低pHに応答して細胞内取り込みが促進されるSAPSペプチド修飾ナノ粒子の機能性評価2013

    • Author(s)
      中山佳代子
    • Organizer
      日本薬剤学会第28年会
    • Place of Presentation
      愛知県名古屋市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腫瘍集積性向上のための腫瘍微弱低pH応答性リポソームの改良と機能性評価2013

    • Author(s)
      森本智士
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] pH応答性ナノ粒子の効率的な細胞質送達メカニズムの解析2013

    • Author(s)
      濱 進
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都府京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] A flexible nano carrier for siRNA delivery into tumor2013

    • Author(s)
      Kogure K
    • Organizer
      40th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      米国ハワイ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Efficient cytoplasmic delivery of siRNA by tumoral pH sensitive nanoparticles via membrane fusion under tumor microenvironment2013

    • Author(s)
      Itakura S
    • Organizer
      40th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      米国ハワイ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 柔軟な構造を有する組織浸透性siRNAキャリアーの開発2013

    • Author(s)
      小暮健太朗
    • Organizer
      第23回アンチセンスシンポジウム
    • Place of Presentation
      徳島県徳島市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of a novel drug delivery system for combination therapy in cancer2012

    • Author(s)
      Hama S. Utsumi S. Nakayama K. Okamura Y. Tsuchiya H. Fukuzawa K. Harashima H. Kogure K
    • Organizer
      第6回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍環境の微弱なpH に応答するペプチドを用いた薬物キャリアーの開発2012

    • Author(s)
      板倉祥子, 濱 進, 中井麻友美, 中山佳代子, 森本智士, 大石利一, 土谷博之, 小暮健太朗
    • Organizer
      第62回日本薬学会近畿支部総会・大会
    • Place of Presentation
      兵庫
    • Related Report
      2013 Final Research Report
  • [Presentation] 抗癌剤トコフェロールコハク酸を用いた新規ドラッグデリバリーシステムの開発2012

    • Author(s)
      濱 進, 土谷博之, 小暮健太朗
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] Develpopment of nobel tumoral pH responsive nanoparticles for cancer therapy2012

    • Author(s)
      Hama S. Itakura S. Nakai M. Nakayama K, Morimoto S. Tsuchiya H. Kogure K
    • Organizer
      the 39th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Quebec city, Canada
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] 組織狭小空間への送達を目指したsiRNA キャリアーの開発2012

    • Author(s)
      小暮健太朗, 島谷悠里, 宇野晃平, 土谷博之, 濱 進
    • Organizer
      第28回日本DDS 学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌治療のための微弱pH 変化応答性薬物キャリアの開発2012

    • Author(s)
      森本智士, 濱 進, 板倉祥子, 中井麻友美, 中山佳代子, 土谷博之, 小暮健太朗
    • Organizer
      第28回日本DDS 学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌治療のための微弱pH変化応答性薬物キャリアの開発2012

    • Author(s)
      森本智士
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 組織狭小空間への送達を目指したsiRNAキャリアーの開発2012

    • Author(s)
      小暮健太朗
    • Organizer
      第28回日本DDS学会学術集会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 抗癌剤トコフェロールコハク酸を用いた新規ドラッグデリバリーシステムの開発2012

    • Author(s)
      濱 進
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腫瘍環境の微弱なpHに応答するペプチドを用いた薬物キャリアーの開発2012

    • Author(s)
      板倉祥子
    • Organizer
      第62回日本薬学会近畿支部総会・大会
    • Place of Presentation
      兵庫県西宮市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of a novel drug delivery system for combination therapy in cancer2012

    • Author(s)
      Hama S.
    • Organizer
      第6回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      京都府京都市
    • Related Report
      2012 Annual Research Report
  • [Presentation] ナノ粒子の膜物性制御による腫瘍低pH下の癌細胞への効率的な薬物送達2011

    • Author(s)
      濱進
    • Organizer
      第9回がんとハイポキシア研究会
    • Place of Presentation
      学習院大学(東京)
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 腫瘍環境応答性ナノキャリアーの開発2011

    • Author(s)
      小暮健太朗、板倉祥子、中井麻由美、中出佳代子、森本智士、濱進
    • Organizer
      第33回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      岡山大学(岡出)
    • Year and Date
      2011-11-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Development of a flexible siRNA carrier penetrable into tumor2011

    • Author(s)
      Kogure K, Shimatani Y, Uno K, Hama S
    • Organizer
      the IUMRS-ICA 2011, 12th International Conferenee in Asia
    • Place of Presentation
      Taipei World Trade Center Nangang Exhibition Hall (TWTC Nangang)(台湾)(招待講演)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] ナノ粒子の膜物性制御による腫瘍低pH下の癌細胞への効率的な薬物送達2011

    • Author(s)
      濱 進
    • Organizer
      第9回がんとハイポキシア研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 腫瘍環境応答性ナノキャリアーの開発2011

    • Author(s)
      小暮健太朗, 板倉祥子, 中井麻由美, 中山佳代子, 森本智士, 濱 進
    • Organizer
      第33回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      岡山
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of a flexible siRNA carrier penetrable into tumor2011

    • Author(s)
      Kogure K, Shimatani Y, Uno K, Hama S
    • Organizer
      the IUMRS-ICA 2011, 12th International Conference in Asia
    • Place of Presentation
      台湾
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://labo.kyoto-phu.ac.jp/bukka/

    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] pH応答性ペプチドを含むナノ粒子2012

    • Inventor(s)
      小暮健太朗, 濱 進
    • Industrial Property Rights Holder
      大鵬薬品工業株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-11-01
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] pH応答性ペプチドを含むナノ粒子2012

    • Inventor(s)
      小暮健太朗、濱進
    • Industrial Property Rights Holder
      大鵬薬品工業株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-11-01
    • Related Report
      2012 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] pH応答性ペプチドを含むナノ粒子2011

    • Inventor(s)
      小暮健太朗, 濱 進
    • Industrial Property Rights Holder
      大鵬薬品工業株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2011-097694
    • Filing Date
      2011-04-25
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] pH応答性ペプチドを含むナノ粒子2011

    • Inventor(s)
      小暮健太朗、濱進
    • Industrial Property Rights Holder
      大鵬薬品工業株式会社
    • Industrial Property Number
      2011-097694
    • Filing Date
      2011-04-05
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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