{
  "abstract": "Precise characterization of proteins and proteoforms within the protein corona is essential for developing safer and more effective nanomedicines for diagnostic and therapeutic applications. Although the protein corona phenomenon has been recognized in nanomedicine for nearly two decades, the application of top-down proteomics to analyze proteoforms within this context has only recently gained traction. In this study, we advance proteoform-level analysis of the protein corona by integrating mass spectrometry (MS)-based top-down proteomics (TDP) and bottom-up proteomics (BUP). TDP analysis of protein corona of polystyrene nanoparticles (PSNPs) identified 3,505 proteoforms of 344 genes in human plasma samples, representing nearly 4-fold improvement in the number of proteoform and gene identifications (IDs) from protein corona of PSNPs and the largest proteoform dataset of protein corona reported so far. BUP analysis of the protein coronas identified 4,570 protein groups, 45,790 peptides, and 23,632 peptides containing modifications in the human plasma samples, representing one of the most comprehensive plasma proteome datasets from BUP to date and over 150% increase in protein IDs compared to previous PSNP-based corona studies. The combination of such large TDP and BUP datasets improves the characterization quality of nearly 35% of identified proteoforms containing mass shifts, producing a more precise proteoform landscape of protein corona. This BUP and TDP combination approach exceeds the capabilities of individual techniques for proteoform characterization in protein corona, and will eventually enhance our understanding of the protein corona and offer valuable insights into nanoparticle-biosystem interactions, as well as advancing proteoform-level biomarker discovery.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Michigan State University, East Lansing, MI, USA",
    "Deming Department of Medicine, Tulane University, New Orleans, LA, USA",
    "Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA",
    "Precision Health Program, Michigan State University, East Lansing, MI, USA",
    "Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden",
    "Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada",
    "Facility for Electron Microscopy Research, McGill University, Montreal, QC, Canada",
    "Deming Department of Medicine, Tulane University, New Orleans, LA, USA. xwliu@tulane.edu",
    "Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA. mahmou22@msu.edu",
    "Precision Health Program, Michigan State University, East Lansing, MI, USA. mahmou22@msu.edu",
    "Department of Chemistry, Michigan State University, East Lansing, MI, USA. lsun@chemistry.msu.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Seyed Amirhossein Sadeghi"
    },
    {
      "affs": [
        1
      ],
      "name": "Kun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifan Yue"
    },
    {
      "affs": [
        0
      ],
      "name": "Reyhane Tabatabaeian Nimavard"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Shaun Grumelot",
      "orcid": "0009-0004-0357-1535"
    },
    {
      "affs": [
        4
      ],
      "name": "Amir Ata Saei",
      "orcid": "0000-0002-2639-6328"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Hojatollah Vali",
      "orcid": "0000-0003-3464-9943"
    },
    {
      "affs": [
        0
      ],
      "name": "Fei Fang",
      "orcid": "0000-0003-0829-9871"
    },
    {
      "affs": [
        7
      ],
      "name": "Xiaowen Liu",
      "orcid": "0000-0003-4139-1127"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Morteza Mahmoudi",
      "orcid": "0000-0002-2575-9684"
    },
    {
      "affs": [
        10
      ],
      "name": "Liangliang Sun",
      "orcid": "0000-0001-8939-5042"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6hxgt8df3qj6k.bib",
  "cited_by": 9,
  "doi": "10.1038/s41467-026-74306-3",
  "fulltext_url": null,
  "id": "6hxgt8df3qj6k",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-74306-3",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "1607|Advanced Proteomics Techniques and Applications"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-74306-3_reference.pdf",
  "pmcid": "PMC12458578",
  "pmid": "41001529",
  "published": "2026-06-11",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/6hxgt8df3qj6k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:44Z",
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      "url": "https://doi.org/10.1038/s41467-026-74306-3"
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  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Advanced Proteomics Techniques and Applications",
      "subfield": "physical"
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  ],
  "title": "Integrated top-down and bottom-up proteomics enables precise characterization of proteoforms within the protein corona",
  "title_text": "Integrated top-down and bottom-up proteomics enables precise characterization of proteoforms within the protein corona",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:03Z",
  "url": "https://research.draconitic.com/paper/6hxgt8df3qj6k",
  "venue": "Nature Communications",
  "versions": []
}