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A self-immolative near-infrared fluorescent probe for identification of cancer cells and facilitating its apoptosis

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Abstract

Hydrogen sulfide (H2S) plays a significant role in the onset and progression of cancer. It has led to increased interest in its potential as a diagnostic tool owing to its overexpression in cancer. However, research into the anti-cancer activity of H2S, particularly its ability to promote apoptosis, is hindered by the lack of effective detection tools. To gain a comprehensive understanding of the targeted efficacy of H2S in promoting cancer cell apoptosis, we designed and synthesized a self-immolative near-infrared fluorescent diagnostic probe, named YH-NO2. The activation of this self-immolative reaction is dependent on the presence of nitroreductase (NTR) overexpressed in tumor cells. The design of YH-NO2 involves releasing fluorophores through the activated self-immolative reaction for detection, while simultaneously releasing H2S-loaded self-immolative spacers to promote cancer cell apoptosis. Consequently, YH-NO2 achieves a seamless integration of recognizing and promoting cancer cell apoptosis through its self-immolative structure. This dual function allows YH-NO2 to recognize NTR activity in cells under varying hypoxia levels and differentiate between normal cells and cancer cells using imaging technology. Notably, YH-NO2 exhibits remarkable stability in cellular environments, providing controlled and selective H2S release, thereby targeting the elimination of cancer cells through the promotion of apoptosis. Furthermore, in vivo experiments have demonstrated that YH-NO2 can accurately identify tumor tissue and effectively reduce its size by utilizing its apoptosis-promoting properties. These findings not only provide further evidence for the anti-cancer activity of H2S but also offer valuable tools for understanding the complex relationship between H2S and cancer.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) Fund (No. U21A20282 and 22174058).

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Authors and Affiliations

  1. State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China

    Jinlong Zhang, Taihe Han, Huipeng Sun, Zehua Han, Xuezhao Shi, Xiaoyan Liu & Haixia Zhang

  2. Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, China

    Jinlong Zhang

  3. GanSu Analysis and Research Center, Lanzhou, 730000, China

    Jun Gao

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  1. Jinlong Zhang
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Correspondence to Haixia Zhang.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

All in vivo experiments were approved for animal testing and evaluated and certified by the Institute for Laboratory Animal Health. Live experiments follow the international welfare guidelines for animal experiments and the "3Rs" principles for experimental animals.

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Zhang, J., Han, T., Sun, H. et al. A self-immolative near-infrared fluorescent probe for identification of cancer cells and facilitating its apoptosis. Anal Bioanal Chem 416, 1529–1540 (2024). https://doi.org/10.1007/s00216-024-05180-5

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  • DOI: https://doi.org/10.1007/s00216-024-05180-5

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