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2023 年度 実績報告書

分子技術を駆使したSN-38二量体設計と新規抗がん用ナノ薬剤の創出

研究課題

研究課題/領域番号 22KF0036
配分区分基金
研究機関東北大学

研究代表者

笠井 均  東北大学, 多元物質科学研究所, 教授 (30312680)

研究分担者 KUMAR SANJAY  東北大学, 多元物質科学研究所, 外国人特別研究員
研究期間 (年度) 2023-03-08 – 2024-03-31
キーワードSN-38 / Homodimer / Disulfide linker / Prodrug / Fabrication / Nanoparticles
研究実績の概要

SN-38 homodimers (9 compounds) and SN-38-indoximod conjugates (with and without disulphide bond) were synthesized in highly efficient yield, followed by fabricated as nano-prodrugs by reprecipitation method. The fabricated nano-prodrug of SN-38 homodimers and SN-38-indoximod conjugate having disulphide bond with 0% and 10% PS80, respectively, were not aggregated in one week stored at 4 °C due disulphide bond may favour the nanoparticle preparation and dispersion stability. Whereas nano-prodrugs of SN-38-indoximod conjugate without disulphide bond with 0/1/10/100% PS80 were aggregated after fabrication. 80-160 nm sized nanoparticles were observed in fabricated nano-prodrugs of SN-38 homodimers and SN-38-indoximod conjugate having disulphide bond (with 10% PS80) in SEM image.
One SN-38 homodimer showed promising in vitro anticancer activity against cancer cells. This result was supported by drug release study under GSH condition in which >85% of SN38 was released from prodrug in 6 h in the presence of GHS. Whereas prodrug SN-38-indoximod conjugate without disulphide didn’t release SN38 under GSH environment due to absence of disulphide bond containing linker. Therefore, it didn’t show in vitro anti-cancer activity against either A549 cells or MCF7 cells.

  • 研究成果

    (1件)

すべて 2023

すべて 学会発表 (1件) (うち国際学会 1件)

  • [学会発表] Fragrance Hedione (methyldihydrojasmonate) from D-Glucose2023

    • 著者名/発表者名
      Sanjay Kumar, Yoshitaka Koseki, Takaaki Kamishima, Hitoshi Kasai
    • 学会等名
      International Symposium for the 80th Anniversary of the Tohoku Branch of the Chemical Society of Japan
    • 国際学会

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公開日: 2024-12-25  

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