{
  "abstract": "The dynamics of the tumor microenvironment (TME) are a key determinant of cancer progres-sion and therapeutic resistance through complex interactions between tumor, stromal and im-mune cell populations. Among these, tumor-associated macrophages (TAMs) play a central role in promoting tumor growth and immune suppression. However, the specific contributions of TAMs remain poorly understood due to the lack of tools enabling selective genetic manipulation in three-dimensional (3D) tumor models. Here, we present a gold nanoparticle-assisted opto-poration approach that enables spatially selective plasmid-based gene delivery to TAMs within intact heterocellular 3D pancreatic ductal adenocarcinoma (PDAC) spheroids, thereby modulat-ing the TME. In two-dimensional (2D) TAM cultures, conventional transfection of IRF5- and IKBKB-encoding plasmids validated their capacity to induce TAM repolarization, as evidenced by activation of interferon signaling. Extending this approach to 3D PDAC spheroids, nanopar-ticle-assisted optoporation achieved selective transfection of TAMs with IRF5- and IKBKB-encoding plasmids by transiently generating nanoscale membrane pores in illuminated cells. TAMs transfection elicited a robust interferon response, marked by transcriptional upregulation of IFNA, IFNB1, and CXCL10, and increased protein levels of IFNB1, IFNL1, and CXCL13, together with downregulation of pro-tumorigenic markers CEACAM5, IL19, and IL32. These coordinated changes indicate a shift towards an anti-tumorigenic TME. By enabling minimally invasive, TAM-specific gene delivery in complex multicellular 3D spheroids, this strategy al-lows precise modulation of the TME and opens new avenues for modeling its dynamics in can-cer progression and therapeutic response.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Ines Poljak"
    },
    {
      "name": "Izzah Nabilah Hussein"
    },
    {
      "name": "Chenlei Gu"
    },
    {
      "name": "Giulio Giustarini"
    },
    {
      "name": "Teng Xiang"
    },
    {
      "name": "Yusuke Toyama"
    },
    {
      "name": "Ciro Chiappini"
    },
    {
      "name": "Giulia Adriani"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dphzydf25eg8t.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.03.16.712123",
  "fulltext_url": null,
  "id": "dphzydf25eg8t",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://hal.science/hal-05776458v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.imm"
    ],
    [
      "hal",
      "2.sdv.imm.ii"
    ],
    [
      "openalex",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7139104413",
  "pdf_url": "https://www.biorxiv.org/content/biorxiv/early/2026/03/18/2026.03.16.712123.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-03",
  "publisher": "BioRxiv",
  "ris": "https://research.draconitic.com/paper/dphzydf25eg8t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:46Z",
      "native_id": "hal-05776458",
      "source": "hal",
      "url": "https://hal.science/hal-05776458v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.imm",
      "subfield": "immunology"
    }
  ],
  "title": "Immune reprogramming of 3D tumor models via optoporation-mediated targeted gene delivery to macrophages",
  "title_text": "Immune reprogramming of 3D tumor models via optoporation-mediated targeted gene delivery to macrophages",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:46Z",
  "url": "https://research.draconitic.com/paper/dphzydf25eg8t",
  "venue": "BioRxiv",
  "versions": []
}