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The Detection of Divalent Iron and Reactive Oxygen Species During Ferroptosis with the Use of a Dual-Reaction Turn-On Fluorescent Probe

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Abstract

Purpose

Ferroptosis, a programmed cell death modality, is an iron-dependent, non-apoptosis pathway that is characterized by the upregulation of divalent iron and reactive oxygen species (ROS) levels. However, the sensitive and rapid detection to track changes in ferroptosis is challenging, partially due to the lack of methods for monitoring the Fe(II) accumulation and ROS generation.

Procedures

Herein, we reported a dual-reaction fluorescent probe DR-1 with turn-on response, which realized the simultaneous visualizing of Fe(II) and ROS with a single probe. The structure of fluorescence quenching group and turn-on fluorophore constitute a double switch for DR-1, which increases its specificity and stability.

Results

During ferroptotic cell death, the upregulation of ROS levels led to the cleavage of quenching group of DR-1, and the aggregation of Fe(II) resulting in fluorescence recovery.

Conclusions

Overall, this study provides a new dual-reaction probe that shows the great potential to explore the mechanism of ferroptosis in vitro and in vivo by fluorescence imaging.

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Acknowledgements

The authors would like to acknowledge the instrumental technical support of the Multimodal Biomedical Imaging Experimental Platform, Institute of Automation, Chinese Academy of Sciences.

The authors would also like to thank Dr. Fudi Wang (Zhejiang University School of Medicine, China) for his critical review of the manuscript.

Funding

This work was supported in part by the National Key Research and Development Program of China under Grants 2017YFA0700401, 2016YFC0103803, and 2017YFA0205200), National Natural Science Foundation of China (grants nos. 62027901, 81227901, 81930053, 81827808, 81527805, 81971198, and 81671851), China Postdoctoral Science Foundation (grant nos. 2020M680301 and 2019TQ0018), Chinese Academy of Sciences Youth Innovation Promotion Association (grant no. 2018167), Chinese Academy of Sciences Key Technology Talent Program, and Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai HLHPTP201703), The Fundamental Research Funds for the Central Universities (grant no. JKF-YG-22-B005).

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Author notes

  1. Yueqi Wang and Changjian Li contributed equally to this work.

Authors and Affiliations

  1. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China

    Yueqi Wang, Jiaming Zhuo, Hui Hui & Jie Tian

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Yueqi Wang, Hui Hui & Jie Tian

  3. School of Engineering Medicine, Beihang University, Beijing, 100191, China

    Changjian Li, Bing Zhou & Jie Tian

  4. Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, 100191, China

    Changjian Li & Jie Tian

  5. Zhuhai Precision Medical Center, Zhuhai People’s Hospital, Affiliated With Jinan University, Zhuhai, 519000, China

    Jie Tian

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  1. Yueqi Wang
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Wang, Y., Li, C., Zhuo, J. et al. The Detection of Divalent Iron and Reactive Oxygen Species During Ferroptosis with the Use of a Dual-Reaction Turn-On Fluorescent Probe. Mol Imaging Biol 25, 423–434 (2023). https://doi.org/10.1007/s11307-022-01774-6

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