The composition of serum is extremely complex, which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis. Recently, nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum. Here, we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona (PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis. We identified 1,070 proteins with a median coefficient of variation of 12.56% using PC-based proteomic analysis, which was twice the number of proteins identified by direct digestion. There were also more biological processes enriched with these proteins. We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis (CIA) rat model treated with methotrexate (MTX). The bioinformatic results indicated that 485 differentially expressed proteins (DEPs) were found in CIA rats, of which 323 DEPs recovered to near normal levels after treatment with MTX. This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies, but also provide more pharmacodynamic biomarkers for disease prediction, diagnosis, and treatment.

血清的成分极其复杂，这使得通过血清蛋白质组发现用于疾病预测和诊断的新药效生物标志物变得复杂。最近，据报道，纳米颗粒可有效降低血清中高丰度蛋白质的比例并富集低丰度蛋白质。在这里，我们合成了一种二氧化硅包覆的氧化铁纳米颗粒，并开发了一种高效且可重复的基于蛋白质电晕 (PC) 的蛋白质组学分析策略，以提高血清蛋白质组学分析的范围。我们使用基于 PC 的蛋白质组学分析鉴定了 1,070 种蛋白质，变异系数中位数为 12.56%，是通过直接消化鉴定的蛋白质数量的两倍。还有更多富含这些蛋白质的生物过程。我们应用这一策略来识别更多的药效学生物标志物，用于用甲氨蝶呤 (MTX) 治疗的胶原性关节炎 (CIA) 大鼠模型。生物信息学结果表明，在 CIA 大鼠中发现了 485 种差异表达蛋白 (DEPs)，其中 323 种 DEPs 在 MTX 处理后恢复到接近正常水平。这一策略不仅可以通过血清蛋白质组学研究帮助我们加深对疾病和药物作用机制的理解，还可以为疾病预测、诊断和治疗提供更多的药效学生物标志物。