Available online 7 August 2022
Highlights•A protein corona-based proteomic analysis strategy was developed for serum proteome.
•This strategy repeatably identified 1,070 serum proteins with broad dynamic range.
•This strategy broadens the serum proteome for pharmacodynamic biomarker exploration.
AbstractThe 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. The biological processes enriched with these proteins were also more. 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 could not only helped enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies, but also provided more pharmacodynamic biomarkers for disease prediction, diagnosis, and treatment.
KeywordsProtein corona
nanoparticles
mass spectrometry
proteomic analysis
pharmacodynamic biomarkers
© 2022 Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.
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