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A ratiometric fluorescent sensor for tracking Cu(I) fluctuation in endoplasmic reticulum

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Abstract

A two-photon ratiometric fluorescent sensor for Cu+ in endoplasmic reticulum (ER), CNSB, was developed via coumarin/ASBD integration based on FRET mechanism. In solution, CNSB shows reversible, highly-specific ratiometric response to Cu+. Moreover, CNSB exhibits suitable Kd value, suggesting the possibility of detecting Cu+ in the living cells. The probe can enter the MCF-7 cells easily and specifically locates in the ER. The highly specific ratiometric response of CNSB toward Cu+ in MCF-7 cells provides the sensor the capacity to visualize both exogenous and endogenous Cu+ in the ER via fluorescence imaging. Next, CNSB was utilized to detect the fluctuation and distribution of Cu+ under ER stress in MCF-7 cells, which confirmed directly the relationship between Cu+ enhancement and ER stress. Meanwhile, the two-photon ability of coumarin facilitated the sensor to visualize Cu+ fluctuation via two-photon fluorescence imaging. In addition, the spatial distribution of Cu+ in the heart slice of the 14-day-old rat was demonstrated using CNSB. This study demonstrates the promising potential of CNSB in clarifying the Cu+-dependent signaling in the ER stress-related diseases.

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Acknowledgements

This work was supported by the National Basic Research Program of China (2015CB856300), the National Natural Science Foundation of China (21571099, 21731004) and the Natural Science Foundation of Jiangsu (BK20150054).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China

    Jungu Guo, Hao Yuan, Yuncong Chen, Zhongyan Chen, Zijian Guo & Weijiang He

  2. Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China

    Menglong Zhao, Liang Zou & Qiang Zhao

  3. Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech), Nanjing, 211816, China

    Yi Liu & Zhipeng Liu

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  1. Jungu Guo
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  2. Hao Yuan
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  3. Yuncong Chen
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Correspondence to Yuncong Chen or Weijiang He.

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Guo, J., Yuan, H., Chen, Y. et al. A ratiometric fluorescent sensor for tracking Cu(I) fluctuation in endoplasmic reticulum. Sci. China Chem. 62, 465–474 (2019). https://doi.org/10.1007/s11426-018-9424-8

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  • DOI: https://doi.org/10.1007/s11426-018-9424-8

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