Surfactant-Modified Magnetic Nanoparticles Enable Efficient and Cost-Effective Plasma Proteomics for Enhanced Biomarker Discovery

The application of more blood proteins into health risk
prediction
and disease diagnostics has long garnered significant interest. However,
comprehensive profiling of proteins in blood samples (plasma or serum),
particularly low-abundance proteins, remains technically challenging
due to the masking effect imposed by high-abundance proteins and the
extraordinarily wide dynamic range of protein abundances. Herein,
we developed an efficient strategy that leveraged the protein corona
formed on surfactant-modified magnetic nanoparticles for the selective
enrichment of low-abundance plasma proteins. Coupled with liquid-chromatography
tandem mass spectrometry (LC-MS/MS) analysis, this strategy allowed
for the detection of over 3500 plasma proteins in a single run, which
was approximately three times and five times more than the number
of proteins detected by the antibody-dependent depletion method and
the direct digestion method, respectively. The application of our
method to an acute myocardial infarction (AMI) cohort and corresponding
healthy control group resulted in the identification of 5000 more
plasma proteins and the discovery of seven potential AMI diagnostic
biomarkers, which showed superior accuracy in diagnosis compared to
conventionally used cardiac troponins. The magnetic nanoparticles
(MNPs) and surfactants are commercially accessible and cost-effective,
and moreover, the modification protocol is simple. These features
ensure the ready adoption of our method by other laboratories, even
those lacking specialized nanotechnology expertise. Additionally,
the magnetic properties of MNPs can further facilitate the smooth
integration with automated sample processing systems, thereby expediting
large-scale clinical studies.

将更多血液蛋白质应用于健康风险预测与疾病诊断领域，长期以来一直受到学界广泛关注。然而，对血液样本（血浆或血清）中的蛋白质进行全面分析，尤其是低丰度蛋白质，仍面临技术挑战——这源于高丰度蛋白质带来的掩蔽效应，以及蛋白质丰度存在极宽的动态范围。
本研究开发了一种高效策略：利用表面活性剂修饰的磁性纳米颗粒上形成的蛋白质冠（protein corona），实现低丰度血浆蛋白质的选择性富集。结合液相色谱-串联质谱（LC-MS/MS）分析，该策略单次检测即可检出超过3500种血浆蛋白质，其检出量分别约为抗体依赖耗竭法和直接消化法的3倍与5倍。
将本方法应用于急性心肌梗死（AMI）队列及对应的健康对照组后，不仅额外鉴定出5000种血浆蛋白质，还发现了7种潜在的急性心肌梗死诊断生物标志物，这些标志物的诊断准确性优于临床常规使用的心肌肌钙蛋白。
磁性纳米颗粒（MNPs）与表面活性剂均可商业化获取且成本低廉，且修饰流程简便。这些特性使得本方法可被其他实验室快速推广应用，即便这些实验室不具备专业纳米技术相关专长。此外，磁性纳米颗粒的磁特性可进一步助力其与自动化样本处理系统的顺畅整合，从而加速大规模临床研究的推进。