A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers

YQ Meng, JY Chen, YQ Liu, YP Zhu, YK Wong, H Lyu, QL Shi, F Xia, LW Gu, XW Zhang, P Gao, H Tang, QY Guo, C Qiu, CC Xu, X He, JZ Zhang, JG Wang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 lowabundance 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.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license
Original languageEnglish
Pages (from-to)879-888
Number of pages10
JournalJournal of Pharmaceutical Analysis
Volume12
Issue number6
Early online dateDec 2022
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • Mass spectrometry
  • Nanoparticles
  • Pharmacodynamic biomarkers
  • Protein corona
  • Proteomic analysis

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