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Selective profiling of liver-related specific proteins based on sofosbuvir-modified magnetic separation material

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Abstract

It has great significance in profiling specific proteins throughout for better understanding of complex pathological processes and in-depth pharmacological studies. In this work, an efficient protein profiling strategy was developed based on the specific protein–drug interaction. Sofosbuvir (SOF), as a first-line drug for the treatment of hepatitis C, was modified onto the surface of nanoparticles through stable chemical bonds to fabricate a novel magnetic separation material denoted as Fe3O4@SiO2@PAA@SOF. With sequence coverage as the screening parameter, nine proteins were profiled from fetal bovine serum (FBS) of which eight were liver related. Similarly, the strategy was applied to hepatocellular carcinoma (HCC) patient serum. Eight proteins were profiled and all of them were liver related, demonstrating the superb specificity and selectivity of this strategy for profiling liver-related proteins by virtue of protein–SOF interaction. When serum proteins from HCC patients were compared to those from healthy people, one unique differential protein (D3DQX7) was profiled, which was liver related and was a potential target for ameliorating liver diseases. For further research, this material design concept and protein profiling strategy can be extended to employ other drugs for corresponding studies.

Graphical abstract

Sofosbuvir, as a therapeutic drug for liver diseases, was modified onto the surface of magnetic nanoparticles to fabricate the specific selective separation material (Fe3O4@SiO2@PAA@SOF). Based on protein–SOF interaction, the material was applied to adsorb specific proteins from different serum samples. After MS analysis, specific proteins, most of which were liver related, were successfully profiled from FBS and HCC patient serum, fully demonstrating the superb specificity and selectivity of this protein profiling strategy.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

Financial support was from National Natural Science Foundation of China (21974045, 82102503), the National Key R&D Program of China (2021YFF0701900), the Science and Technology Commission of Shanghai Municipality (No. 19142201100, 6142200500), the Fundamental Research Funds for the Central Universities (No. JKJ01221718), and Zhongshan Hospital Fudan University Youth Foundation (2020ZSQN30).

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Authors and Affiliations

  1. Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China

    Yini Pan, Sen Xu, Lingyi Zhang & Weibing Zhang

  2. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Zhenxin Wang

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  1. Yini Pan
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Correspondence to Lingyi Zhang or Weibing Zhang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of Zhongshan Hospital Fudan University.

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Pan, Y., Wang, Z., Xu, S. et al. Selective profiling of liver-related specific proteins based on sofosbuvir-modified magnetic separation material. ANAL. SCI. 39, 313–323 (2023). https://doi.org/10.1007/s44211-022-00238-9

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