{
  "abstract": "Since 2018, ionizable lipid nanoparticles (LNPs) have revolutionized nucleic acid therapeutics. However, achieving potent extrahepatic delivery remains a formidable challenge, primarily due to rapid hepatic uptake driven by apolipoprotein adsorption. While analyzing the LNP protein corona is essential for engineering organ-specific tropism, these soft materials present unique analytical hurdles. Co-isolation of blood-borne contaminants, such as extracellular vesicles and lipoproteins, often masks the true corona composition. This perspective examines the critical need for refined proteomic strategies to distinguish genuine corona proteins from impurities. We propose tailored investigative approaches, suggesting the LNP protein corona significantly differs from the rigid shells observed on inorganic nanoparticles. Engineering organ-specific LNPs requires a deep understanding of the protein corona, yet its fluid nature makes analysis difficult. This perspective identifies how blood contaminants mask true corona composition and advocates for refined strategies to study these unique lipid-protein interfaces.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA. babak@chemistry.msu.edu",
    "Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, 171 77, Sweden",
    "Department of Chemistry, Michigan State University, East Lansing, MI, 48824, USA",
    "Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA",
    "Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA",
    "Department of Anatomy and Cell Biology, McGill University, Montreal, QC, H3A 0C7, Canada",
    "Facility for Electron Microscopy Research, McGill University, Montreal, QC, H3A 0C7, Canada",
    "Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. kawhite@andrew.cmu.edu",
    "Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. kawhite@andrew.cmu.edu",
    "Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, 48823, USA. mahmou22@msu.edu",
    "Precision Health Program, Michigan State University, East Lansing, MI, 48823, USA. mahmou22@msu.edu"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Babak Borhan",
      "orcid": "0000-0002-3193-0732"
    },
    {
      "affs": [
        1
      ],
      "name": "Amanda M. Murray",
      "orcid": "0009-0000-2124-351X"
    },
    {
      "affs": [
        2
      ],
      "name": "Amir Ata Saei",
      "orcid": "0000-0002-2639-6328"
    },
    {
      "affs": [
        3
      ],
      "name": "Bahareh Ghaffari",
      "orcid": "0000-0003-0126-334X"
    },
    {
      "affs": [
        3
      ],
      "name": "James E. Jackson",
      "orcid": "0000-0002-4506-7415"
    },
    {
      "affs": [
        4
      ],
      "name": "Naseeha Mohammed",
      "orcid": "0009-0007-6680-1133"
    },
    {
      "affs": [
        5,
        6,
        7,
        1,
        8,
        9,
        10
      ],
      "name": "Michael J. Mitchell",
      "orcid": "0000-0002-3628-2244"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Hojatollah Vali",
      "orcid": "0000-0003-3464-9943"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Kathryn A. Whitehead",
      "orcid": "0000-0002-0100-7824"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Morteza Mahmoudi",
      "orcid": "0000-0002-2575-9684"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5v9srhgpn22zb.bib",
  "cited_by": 11,
  "doi": "10.1038/s41467-026-74240-4",
  "fulltext_url": null,
  "id": "5v9srhgpn22zb",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-74240-4",
  "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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      "1312|RNA Interference and Gene Delivery"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-74240-4.pdf",
  "pmcid": "PMC13263340",
  "pmid": "42285973",
  "published": "2026-06-12",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/5v9srhgpn22zb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W7164553793",
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      "url": "https://doi.org/10.1038/s41467-026-74240-4"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Interference and Gene Delivery",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Influence of protein aggregates, extracellular vesicles, and lipoprotein fusion on ionizable lipid nanoparticles protein corona analysis",
  "title_text": "Influence of protein aggregates, extracellular vesicles, and lipoprotein fusion on ionizable lipid nanoparticles protein corona analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:07Z",
  "url": "https://research.draconitic.com/paper/5v9srhgpn22zb",
  "venue": "Nature Communications",
  "versions": []
}