{
  "abstract": "DNA tetrahedra (DNA Td) are promising nanocarriers for drug delivery, but how hypoxia affects their cellular internalisation remains poorly understood. We synthesised and characterised Cy5-labelled DNA Td and established chemical hypoxia; in HeLa, MDA-MB-231, and MCF-7 cells. Hypoxia was confirmed by HIF-1; nuclear translocation. Confocal microscopy revealed significantly reduced DNA Td uptake under hypoxia, whereas transferrin and cholera toxin B uptake increased, indicating cargo-selective regulation. Temperature-arrest experiments confirmed reduced energy-dependent internalisation. Pharmacological profiling showed a shift from clathrin-mediated and galectin/glycan-dependent pathways toward lipid raft/cholesterol-dependent uptake. Hypoxia increased plasma membrane electronegativity, suggesting a biophysical barrier to DNA Td uptake. Importantly, DOTMA complexation restored uptake to normoxic levels, identifying electrostatic repulsion as a key determinant. In zebrafish larvae, hypoxia significantly enhanced whole-larva DNA Td accumulation. These findings highlight surface charge engineering as a strategy for improving DNA nanostructure delivery under hypoxic conditions.",
  "abstract_shown": true,
  "affiliations": [
    "Indian Institute of Technology Gandhinagar"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "S. Kosara"
    },
    {
      "name": "G. Prakash"
    },
    {
      "name": "H. Dave"
    },
    {
      "name": "S. Dhanasekaran"
    },
    {
      "affs": [
        0
      ],
      "name": "D. D. Bhatia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eejxnvr8t2p0f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.02.748847",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748847v1.full",
  "id": "eejxnvr8t2p0f",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748847v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7210287447",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748847v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eejxnvr8t2p0f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:40Z",
      "native_id": "10.64898/2026.09.02.748847",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748847v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Hypoxia Induced Modulation of Cellular and in vivo uptake of DNA nanocage implications in therapeutics",
  "title_text": "Hypoxia Induced Modulation of Cellular and in vivo uptake of DNA nanocage implications in therapeutics",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:40Z",
  "url": "https://research.draconitic.com/paper/eejxnvr8t2p0f",
  "venue": "bioRxiv",
  "versions": []
}