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<p>The specific trigger of tumor cell ferroptosis is an effective way for precise cancer therapy with low side effects and high efficiency. However, the trigger reagents should be further developed. Herein, an ATT ((<i>E</i>)-2,2′-(((1,2-diphenylethene-1,2-diyl) bis(4,1-phenylene))bis(2-(4-(dicyanomethylene)-2,3,5,6-tetrafluorocyclohexa-2,5-dien-1-ylidene)-2-(4-(diphenylamino)phenyl) ethan-1-yl-1-ylidene))dimalononitrile) reagent bearing cyano and perfluorophenyl groups was found to be a capable reaction with cysteine (Cys) based on a single electron transfer (SET) mechanism in a concentration-dependent manner. Remarkably, with the depletion of Cys, the synthesis of glutathione (GSH) is inhibited intracellularly, which leads to ferroptosis and enhances the sensitivity of tumor cells towards paclitaxel, resulting in efficient inhibition of tumor cells. Meanwhile, the fluorescence of the system is enhanced significantly by destroying the intramolecular charge transfer process of ATT after its reaction with Cys, realizing the self-indication of the treatment. Based on this synergistic treatment, the efficient and specific suppression of tumor cells both <i>in vitro</i> and <i>in vivo</i> is realized, providing a reliable and promising strategy for cancer treatment in the clinic.</p>

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A reactive and self-indication reagent for selective tumor inhibition by triggering ferroptosis and synergistically enhancing chemosensitivity

  • 期刊论文

  • 发表日期：

    2025年6月27日

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  • Guiquan Zhang,
  • Pengbo Han,
  • He Xu,
  • Daming Zhou,
  • Chunyang Li,
  • Rui Hua,
  • Rong Hu,
  • Anjun Qin,
  • Ben Zhong Tang

摘要

The specific trigger of tumor cell ferroptosis is an effective way for precise cancer therapy with low side effects and high efficiency. However, the trigger reagents should be further developed. Herein, an ATT ((E)-2,2′-(((1,2-diphenylethene-1,2-diyl) bis(4,1-phenylene))bis(2-(4-(dicyanomethylene)-2,3,5,6-tetrafluorocyclohexa-2,5-dien-1-ylidene)-2-(4-(diphenylamino)phenyl) ethan-1-yl-1-ylidene))dimalononitrile) reagent bearing cyano and perfluorophenyl groups was found to be a capable reaction with cysteine (Cys) based on a single electron transfer (SET) mechanism in a concentration-dependent manner. Remarkably, with the depletion of Cys, the synthesis of glutathione (GSH) is inhibited intracellularly, which leads to ferroptosis and enhances the sensitivity of tumor cells towards paclitaxel, resulting in efficient inhibition of tumor cells. Meanwhile, the fluorescence of the system is enhanced significantly by destroying the intramolecular charge transfer process of ATT after its reaction with Cys, realizing the self-indication of the treatment. Based on this synergistic treatment, the efficient and specific suppression of tumor cells both in vitro and in vivo is realized, providing a reliable and promising strategy for cancer treatment in the clinic.