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2023 年度 実績報告書

Precisely activating ferroptosis by Fe(II)-triggered drug release for enhanced cancer therapy

研究課題

研究課題/領域番号 22K20530
研究機関京都大学

研究代表者

MU Huiying  京都大学, 工学研究科, 助教 (80967399)

研究期間 (年度) 2022-08-31 – 2024-03-31
キーワードFe2+ / fluorescent dye / cleavage / pH-responsive / tumor imaging
研究実績の概要

In the year of FY2023, we prepared various molecules to evaluate the Fe2+-triggered reaction based on this project. The oxime ester was used as a promising cleavage linker for fluorescent dye with a tunable substituent. And we evaluated the effects of various substituents on the Fe2+-mediated reactions, including electron-donated/withdrawing moieties and FRET-paired fluorophores, and etc. The fluorescence output of probes was chosen to investigate their cleavage of oxime ester by Fe2+ in various conditions. It was hound that a good ratiometric properties of the FRET-type probe was achieved upon the activation of Fe2+. However, the stability of probe should be furtherly adjusted due to its high electron-withdrawing property of substituent. This research will be continued to conduct in the future.
In addition, we designed and developed a fluorescent sensor CypH2S with a pH-sensitive cyclic substructure for detection of acidic tumor microenvironment. Upon pH variation, the sensor underwent structural changes: the closed-ring form, CypH2S-C, exhibited suppressed dye aggregation, while the open-ring form, CypH2S-O, tended to aggregate in aqueous solutions under slightly acidic conditions. Importantly, CypH2S facilitated rapid and selective tumor visualization in a living mouse model via fluorescence imaging of its pH-responsive aggregation with a 1.9-fold tumor/background ratio less than 1 hour. Furthermore, prompt clearance of CypH2S from the bloodstream post-tumor detection. This work also pubished in the journal of Sensors and Actuators B: Chemical with a high evaluation.

  • 研究成果

    (8件)

すべて 2024 2023

すべて 雑誌論文 (4件) (うち国際共著 4件、 査読あり 4件) 学会発表 (2件) (うち国際学会 2件) 産業財産権 (2件) (うち外国 1件)

  • [雑誌論文] A reductively convertible nickel phthalocyanine precursor as a biological thiol-responsive turn-on photoacoustic contrast agent2024

    • 著者名/発表者名
      Nogita Kohei、Sugahara Takaya、Miki Koji、Mu Huiying、Kobayashi Minoru、Harada Hiroshi、Ohe Kouichi
    • 雑誌名

      Chemical Communications

      巻: 60 ページ: 1472~1475

    • DOI

      10.1039/D3CC05628G

    • 査読あり / 国際共著
  • [雑誌論文] Light-controllable cell-membrane disturbance for intracellular delivery2024

    • 著者名/発表者名
      Huo Wenting、Miki Koji、Mu Huiying、Osawa Takashi、Yamaguma Harumi、Kasahara Yuuya、Obika Satoshi、Kawaguchi Yoshimasa、Hirose Hisaaki、Futaki Shiroh、Miyazaki Yusuke、Shinoda Wataru、Akai Shuji、Ohe Kouichi
    • 雑誌名

      Journal of Materials Chemistry B

      巻: in press ページ: in press

    • DOI

      10.1039/D3TB02956E

    • 査読あり / 国際共著
  • [雑誌論文] Fast Tumor Imaging Using pH-Responsive Aggregation of Cyanine Dyes with Rapid Clearance2024

    • 著者名/発表者名
      Huiying Mu, Shuai Shao, Bingquan Wu, Koji Miki, Minoru Kobayashi, Hiroshi Harada, and Kouichi Ohe
    • 雑誌名

      Sensors and Actuators B Chemical

      巻: in press ページ: in press

    • DOI

      10.1016/j.snb.2024.135876

    • 査読あり / 国際共著
  • [雑誌論文] Photoacoustic signal enhancement of Al- and Si-Phthalocyanines caused by photoinduced cleavage of water-soluble axial ligand2023

    • 著者名/発表者名
      Nogita Kohei、Miki Koji、Imaizumi Naoto、Oe Masahiro、Mu Huiying、Ohe Kouichi
    • 雑誌名

      Journal of Photochemistry and Photobiology A: Chemistry

      巻: 438 ページ: 114547~114547

    • DOI

      10.1016/j.jphotochem.2023.114547

    • 査読あり / 国際共著
  • [学会発表] pH-Activatable Cyanine Dyes for Selective Tumor Bioimaging in Living Mice2024

    • 著者名/発表者名
      Huiying Mu, Shuai Shao, Koji Miki, Hiroshi Harada, Kouichi Ohe
    • 学会等名
      the 3rd International Symposium on Biofunctional Chemistry (ISBC2024)
    • 国際学会
  • [学会発表] Selective Tumor Imaging in Living Mice Using Near-Infrared pH-Activatable Cyanine Dyes2023

    • 著者名/発表者名
      Huiying Mu, Shuai Shao, Koji Miki, Kouichi Ohe
    • 学会等名
      the 15th International Kyoto Conference on New Aspects of Organic Chemistry
    • 国際学会
  • [産業財産権] 新規化合物、細胞膜透過促進剤及び化合物の細胞膜内部への導入方法2023

    • 発明者名
      三木康嗣,ブンテイホー,ホイインムー,川口祥正,広瀬久昭
    • 権利者名
      三木康嗣,ブンテイホー,ホイインムー,川口祥正,広瀬久昭
    • 産業財産権種類
      特許
    • 産業財産権番号
      2023-146159
  • [産業財産権] 特定条件下で発光する化合物、および、該化合物を用いたがん幹細胞の検出方法2023

    • 発明者名
      三木康嗣,麻植雅裕,鈴木叶瑛,MUHuiying
    • 権利者名
      三木康嗣,麻植雅裕,鈴木叶瑛,MUHuiying
    • 産業財産権種類
      特許
    • 産業財産権番号
      PCT/JP2023/47011
    • 外国

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公開日: 2024-12-25  

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