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Improvement of the surface properties of nanoparticles by using a novel stealth device and their application to nucleic acid carrier controlling tumor microenvironment.

Research Project

Project/Area Number 18H03540
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

Hama Susumu  京都薬科大学, 薬学部, 講師 (60438041)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
KeywordsDDS / 腫瘍微小環境 / 血中滞留性 / 癌微小環境 / ポレチレングリコール(PEG)ジレンマ / がん微小環境
Outline of Final Research Achievements

Liposomal nucleic acid carrier in response to tumor microenvironment has been developed by the surface modification of a novel blood circulating device TGL. Slightly acidic pH sensitive peptide (SAPSP)-modified liposomes showed pH-sensitivity even when the surface hydrophilicity was increased by modifying TGL on their surface. When plasmid DNA was encapsulated into TGL-modified SAPSP-lipo, the expression of exogenous gene in cancer cells was enhanced in response to slightly acidic pH. In tumor penetration type SAPSP (SAPSP-iRGD)-modified liposomes, the tumor penetration of SAPSP-iRGD-lipo was enhanced by their surface modification of TGL. Furthermore, Akt inhibitor encapsulated into TGL-SAPSP-iRGD-lipo induced cell death at slightly acidic pH. Therefore, TGL is a novel blood circulating device capable of improving the surface properties of nanoparticles without inhibiting the function of tumor microenvironment-responsive drug carrier.

Academic Significance and Societal Importance of the Research Achievements

現在の癌治療ドラッグデリバリーシステムの開発において、癌への受動的送達のために血中滞留性素子のポリエチレングリコール(PEG)をナノ粒子型キャリアーの表面に修飾する必要がある。しかし、PEG修飾はナノ粒子の細胞内取り込みを阻害することが課題である。本研究で開発した新規血中滞留性素子TGLは、ナノ粒子の細胞内取り込みを阻害しないだけでなく、各種機能性ナノ粒子の機能を維持することが可能である。そのため、TGLはPEGに取って代わる新規血中滞留性素子として、広く医薬品開発へ応用されることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (6 results)

All 2020 2019 2018 Other

All Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Presentation] 腫瘍低pH応答性リポソームの表面改質による血中滞留性の向上2020

    • Author(s)
      濱 進、板倉祥子、前田静香、丸川裕己、宗 慶太郎
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血中滞留性と腫瘍低pH応答性を併せ持つDDSの開発2019

    • Author(s)
      濱 進、丸川裕己、板倉祥子、宗 慶太郎
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規血中滞留性素子を修飾した腫瘍微小環境応答性リポソームの開発2019

    • Author(s)
      濱 進、板倉祥子、宗 慶太郎
    • Organizer
      第41回日本バイオマテリアル学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ポリエチレングリコール修飾リポソームと微弱低pH応答性ペプチド修飾リポソームの血中滞留性の比較2019

    • Author(s)
      渡邊 優哉,中山 佳代子,中井 麻友美,丸川 裕己,小暮 健太朗,濱 進
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of a siRNA Carrier Penetrable into the Deep Region of Tumor2018

    • Author(s)
      Hama S, Itakura S, Kogure K
    • Organizer
      BIT's 9th World Gene Convention 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 京都薬科大学薬品物理化学分野

    • URL

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

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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