{
  "abstract": "Lipid nanoparticles (LNPs) are central to nanomedicine, yet their clinical translation is limited by the difficulty of predicting structure-bioactivity relationships. Although the biomolecular corona is known to define the nanoparticle biological identity by modifying surface properties, its effect on internal nanoparticle organization remains largely unexplored. Since the internal lipid organization of LNPs governs key properties, including stability, cargo protection, internalization and intracellular trafficking, understanding this coupling is critical to correlate synthetic design to therapeutic outcome. Here, combining structural and mechanistic evidence, we show that plasma lipoproteins engage in molecular-scale lipid exchange with the LCNP membrane, rather than persisting as an adsorbed layer of intact particles, actively remodeling the internal nanoparticle structure. Using model lipid liquid-crystalline nanoparticles with well-defined cubic and inverse hexagonal phases, we systematically investigate how lipoproteins modulate LNP structure. Combining fluorescence nanoparticle tracking, synchrotron small-angle X-ray scattering, cryo-electron microscopy, and neutron reflectometry with isotopic contrast matching, we provide evidence of lipoprotein-driven lipid transfer and phase reorganization at the nanoscale. We observe a phase-selective response: inverse hexagonal LNPs remain structurally stable despite lipid exchange, whereas cubic LNPs undergo pronounced remodeling, including significant change in size and lattice ordering. These transformations correlate with distinct cellular uptake profiles. Our findings suggest that in soft lipid nanoparticles, the biological identity commonly described as a biomolecular corona is not merely a surface event but an interface-mediated process that reshapes the nanoparticle internal structure, with direct implications for next-generation nanomedicine design.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry \"Ugo Schiff\", University of Florence, 50019Sesto Fiorentino, Florence, Italy.",
    "CSGI, Center for Colloid and Surface Science, 50019Sesto Fiorentino, Florence, Italy.",
    "European Laboratory for Non-Linear Spectroscopy, Via Nello Carrara 1, 50019Sesto Fiorentino, Italy.",
    "National Institute of Optics─National Research Council, Via Nello Carrara 1-I, 50019Sesto-Fiorentino, Firenze, Italia.",
    "ETH Zürich, Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, 8093Zürich, Switzerland.",
    "EYE-Lab, Institute of Applied Sciences and Intelligent Systems, National Research Council, Via Pietro Castellino 111, 80131Napoli, Italy.",
    "European Spallation Source ERIC, P.O. Box 176, SE 22100Lund, Sweden.",
    "Institut Laue-Langevin, 71 Avenue des Martyrs, CS20156, 38042Grenoble, France."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lucrezia Caselli",
      "orcid": "0000-0001-5293-8816"
    },
    {
      "affs": [
        2
      ],
      "name": "Marta Rojas-Rodríguez"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Valentina Pacciani",
      "orcid": "0009-0000-9931-6256"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Martino Calamai",
      "orcid": "0000-0002-4031-7235"
    },
    {
      "affs": [
        4
      ],
      "name": "Roberto Frigerio"
    },
    {
      "affs": [
        4
      ],
      "name": "Andrea Zendrini"
    },
    {
      "affs": [
        5
      ],
      "name": "Gennaro Sanità"
    },
    {
      "affs": [
        5
      ],
      "name": "Emanuela Esposito",
      "orcid": "0000-0002-5347-247X"
    },
    {
      "affs": [
        6
      ],
      "name": "Anna Leung",
      "orcid": "0000-0002-8196-9774"
    },
    {
      "affs": [
        6
      ],
      "name": "Hanna Wacklin-Knecht"
    },
    {
      "affs": [
        7
      ],
      "name": "Ben Humphreys"
    },
    {
      "affs": [
        4
      ],
      "name": "Paolo Arosio"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jacopo Cardellini"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Debora Berti",
      "orcid": "0000-0001-8967-560X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/698ry1qws1jk1.bib",
  "cited_by": 0,
  "doi": "10.1021/acsnano.6c09400",
  "fulltext_url": "https://europepmc.org/articles/PMC13585173",
  "id": "698ry1qws1jk1",
  "issns": [
    "1936-0851",
    "1936-086X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42915048",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2502|Nanoparticle-Based Drug Delivery"
    ]
  ],
  "openalex": "W7207777000",
  "pdf_url": "https://europepmc.org/articles/PMC13585173?pdf=render",
  "pmcid": "PMC13585173",
  "pmid": "42915048",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/698ry1qws1jk1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42915048",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42915048"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2502|Nanoparticle-Based Drug Delivery",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Lipoprotein Corona Reshapes the Internal Structure of Lipid Nanoparticles.",
  "title_text": "Lipoprotein Corona Reshapes the Internal Structure of Lipid Nanoparticles.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/698ry1qws1jk1",
  "venue": "ACS nano",
  "versions": []
}