{
  "abstract": "Surface charge is widely regarded as a primary determinant of nanoparticle–immune cell interactions, yet nanocarriers with similar physicochemical profiles often exhibit markedly different biological outcomes. Here, we show that ligand conformational diversity, quantified through an information-theoretic descriptor (Hligand), is strongly associated with a regime transition in the relationship between surface charge and cellular uptake. Analysis of 105 gold nanoparticles from a benchmark protein corona dataset identifies a critical threshold at Hligand*≈1.76 bits (F = 47.3, p < 10−14): below this value, zeta potential is positively associated with uptake (r = +0.70), whereas above it the relationship reverses (r=−0.58), consistent with steric shielding by flexible surface ligands. Entropy-derived descriptors improve predictive performance across multiple model classes (ΔR2 up to +0.118), with gains concentrated in high-entropy regimes where physicochemical descriptors alone are insufficient. An analytical competition model captures this transition in a compact form (R2 = 0.550), with 2H*≈3.4 effective microstates marking a numerical balance point between electrostatic and steric contributions. Cross-dataset validation on 652 multi-material nanoparticles supports transferability of the descriptor framework (ΔR2=+0.181). We emphasize that Hligand is a constructed information-theoretic descriptor rather than a thermodynamic entropy, and that all findings are derived from retrospective analysis of in vitro datasets and not from controlled experimental manipulation. The identified threshold therefore represents a reproducible statistical pattern and a testable hypothesis for how ligand flexibility modulates interaction regimes. This framework provides a computable basis for organizing nanocarrier design hypotheses and motivates prospective validation in more complex carrier systems.",
  "abstract_shown": true,
  "affiliations": [
    "Clevix Lab, Clevix LLC, Hanoi, Vietnam"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Quynh Hoa Truong"
    },
    {
      "name": "Xuan Khanh Truong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bstga2qt5ab4p.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358239",
  "fulltext_url": null,
  "id": "bstga2qt5ab4p",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358239",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2502|Nanoparticle-Based Drug Delivery"
    ],
    [
      "plos",
      "/Biology and life sciences/Bioengineering/Biotechnology/Bionanotechnology"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells"
    ],
    [
      "plos",
      "/Engineering and technology/Bioengineering/Biotechnology/Bionanotechnology"
    ],
    [
      "plos",
      "/Engineering and technology/Nanotechnology/Bionanotechnology"
    ],
    [
      "plos",
      "/Engineering and technology/Nanotechnology/Nanomaterials/Nanocarriers"
    ],
    [
      "plos",
      "/Engineering and technology/Nanotechnology/Nanoparticles"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells"
    ],
    [
      "plos",
      "/Physical sciences/Materials science/Materials/Nanomaterials/Nanocarriers"
    ],
    [
      "plos",
      "/Physical sciences/Mathematics/Discrete mathematics/Combinatorics/Permutation"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Electricity/Electrostatics"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Thermodynamics"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Thermodynamics/Entropy"
    ]
  ],
  "openalex": "W7213544310",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358239&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/bstga2qt5ab4p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pone.0358239",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358239"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "biology",
      "origin": "plos:biotechnology",
      "subfield": "systems-synthetic"
    },
    {
      "field": "physics",
      "origin": "plos:thermodynamics",
      "subfield": "statistical-nonlinear"
    }
  ],
  "title": "Ligand conformational entropy as a regime-switching descriptor of the electrostatic–uptake relationship in nanocarrier–immune cell interactions",
  "title_text": "Ligand conformational entropy as a regime-switching descriptor of the electrostatic–uptake relationship in nanocarrier–immune cell interactions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/bstga2qt5ab4p",
  "venue": "PLOS One",
  "versions": []
}