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.