{
  "abstract": "Cytokine-based immunotherapy holds considerable promise for cancer treatment, but its clinical translation is constrained by systemic toxicity, rapid clearance, and limited tumor selectivity. Here, we engineered a modular dextran–lipid nanoplatform that integrates biomaterial design with bioorthogonal surface functionalization for tumor-responsive cytokine delivery (Fig. 1). Azide-functionalized dextran was chemically modified to tune its physicochemical properties and subsequently assembled with an ionizable lipidoid to form hybrid nanoparticles with reactive surface handles. Pro-inflammatory cytokines were covalently displayed on the nanoparticle surface through strain-promoted azide–alkyne cycloaddition, followed by installation of an enzyme-cleavable linker and a PEG-based steric shield. In the tumor microenvironment, tumor-associated proteases cleave the linker, removing the shielding layer and restoring accessibility of the surface-bound cytokine without requiring its complete release from the carrier, as schematically illustrated in Fig. 1. Using IL-18 as a model cytokine, the platform enabled efficient surface conjugation while preserving cytokine bioactivity, and enzyme-triggered de-shielding resulted in time-dependent recovery of biological activity in vitro. The nanoparticles also exhibited good colloidal stability and biocompatibility under the investigated conditions. Overall, this work establishes a modular biomaterial platform in which programmable surface chemistry enables controlled cytokine presentation and tumor-responsive activation, providing a versatile strategy for localized protein-based immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Health Technology",
    "Technical University of Denmark",
    "Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, Copenhagen, Denmark, DK-2100",
    "National Centre for Nanofabrication and Characterization",
    "Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark, DK-2100"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jing Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tao Zheng"
    },
    {
      "affs": [
        2
      ],
      "name": "José Moreira"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Murat Nulati Yesibolati"
    },
    {
      "affs": [
        4
      ],
      "name": "Mingshi Yang"
    },
    {
      "affs": [
        4
      ],
      "name": "Holger Grohganz"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yi Sun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/13qtmz78edmxw.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008224/v1",
  "fulltext_url": null,
  "id": "13qtmz78edmxw",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008224/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2502|Nanoparticle-Based Drug Delivery"
    ]
  ],
  "openalex": "W7207539597",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008224/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/13qtmz78edmxw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008224",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008224/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2502|Nanoparticle-Based Drug Delivery",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Biomaterial and bioorthogonal surface engineering of a modular dextran–lipid nanoplatform for tumorresponsive cytokine delivery",
  "title_text": "Biomaterial and bioorthogonal surface engineering of a modular dextran–lipid nanoplatform for tumorresponsive cytokine delivery",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:17Z",
  "url": "https://research.draconitic.com/paper/13qtmz78edmxw",
  "venue": "ChemRxiv",
  "versions": []
}