4.7 Article

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

Journal

JOURNAL OF PHARMACEUTICAL ANALYSIS
Volume 12, Issue 6, Pages 879-888

Publisher

ELSEVIER
DOI: 10.1016/j.jpha.2022.07.002

Keywords

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

Funding

  1. National Key Research and Development Program of China [2020YFA0908000, 2020YFE0205100]
  2. Innovation Team and Talents Cultivation Program of National Administration of Tradi-tional Chinese Medicine [ZYYCXTD-C-2020 02]
  3. National Natural Science Foundation of China [82074098, 82173914, 82141001]
  4. CACMS Innovation Fund [CI2021A05101, CI2021A05104]
  5. Fundamental Research Funds for the Central Public Welfare Research Institutes [ZZ15-YQ-065, ZZ14-YQ-058, ZZ14-YQ-050, ZZ14-YQ-051, ZZ14-YQ-052, ZZ14-ND-010, ZZ15-ND-10, ZZ14-FL-0 02]
  6. Chinese Academy of Sciences [YJKYYQ20210025]

Ask authors/readers for more resources

The composition of serum is highly complex, making the discovery of new pharmacodynamic biomarkers challenging. This study developed a nanoparticle-based proteomic analysis strategy to enhance the range of serum proteomic analysis. The strategy successfully identified more proteins and enriched biological processes, providing potential pharmacodynamic biomarkers for disease prediction, diagnosis, and treatment.
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 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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