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

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. 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.