{
  "abstract": "Glucocorticoids (GCs) are highly effective therapies for inflammatory diseases, but their clinical use is severely limited by systemic toxicities. To address this liability, we developed a modular antibody–drug conjugate (ADC) platform for targeted delivery of GC to immune cells, thereby minimizing systemic exposure to free GC. The platform integrates three key design features: (i) fluticasone furoate (FF), a potent metabolically soft glucocorticoid; (ii) a legumain-cleavable AsnAsnGlyPro self-immolative linker for lysosome-selective payload release; and (iii) C11 hydroxyl conjugation to enhance resistance to serum esterase-mediated hydrolysis. ADCs targeting TNFα, CD38, and CD11a exhibited nanomolar potency in glucocorticoid-responsive reporter assays and excellent serum stability enabled by the C11 conjugation. Across all three targets, the ADCs displayed nanomolar potency in glucocorticoid-responsive reporter assays, achieving over 50-fold selectivity over non-targeting isotype controls. Functional assays in primary bone marrow-derived macrophages (BMDMs) and THP-1 cells confirmed potent inhibition of NF-κB signaling and pro-inflammatory cytokine secretion (IL-6, IL-8). Extensive stability assays in human and mouse serum revealed that the C11-conjugated constructs are highly resistant to premature cleavage. These findings establish a robust, highly stable soft glucocorticoid ADC platform for targeted immunosuppression with the potential to improve the safety and efficacy of glucocorticoid therapy for inflammatory diseases.",
  "abstract_shown": true,
  "affiliations": [
    "School of Pharmacy and Pharmaceutical Sciences, Binghamton University PO Box 6000 Binghamton NY 13902-6000 USA +1 (845)234 9113"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Aiman A. Yaseen"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel J. Cohen"
    },
    {
      "affs": [
        0
      ],
      "name": "Anqi Zhang",
      "orcid": "0000-0002-7158-4256"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Nathan Tumey",
      "orcid": "0000-0001-8890-7018"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/664306ppd0g5z.bib",
  "cited_by": 0,
  "doi": "10.1039/d6md00649c",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728932/?tool=EBI",
  "id": "664306ppd0g5z",
  "issns": [
    "2632-8682"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13728932",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "2403|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7221801039",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728932/pdf/?tool=EBI",
  "pmcid": "PMC13728932",
  "pmid": "42979242",
  "published": "2026-10-14",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/664306ppd0g5z.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:45Z",
      "native_id": "PMC:PMC13728932",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13728932"
    },
    {
      "first_seen": "2026-11-07T12:21:48Z",
      "native_id": "PMC13728932",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6md00649c"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "immunology"
    }
  ],
  "title": "C11-conjugated soft glucocorticoid antibody–drug conjugates for precision immunomodulation",
  "title_text": "C11-conjugated soft glucocorticoid antibody–drug conjugates for precision immunomodulation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:48Z",
  "url": "https://research.draconitic.com/paper/664306ppd0g5z",
  "venue": "RSC medicinal chemistry",
  "versions": []
}