{
  "abstract": "Introduction\n\nExcessive proliferation of invasive fibroblast-like synoviocytes (FLS) and persistent synovial inflammation inevitably drive the pathological progression of rheumatoid arthritis (RA). A drug delivery system enabling dual regulation of macrophages and FLS is highly desirable for RA treatment.Methods\n\nWe fabricated microenvironment-triggered sequentially targeted micelles (HAP@CMR) co-loaded with ginsenoside Rg1 (Rg1) and celastrol (Cel) for dual regulation of macrophages and FLS. Rg1 was conjugated to the micelle surface via a ROS-responsive linker. Within the ROS-overexpressing joint microenvironment, ROS-triggered cleavage of the Rg1 shell unmasked the HAP-1 targeting peptide to facilitate FLS endocytosis alongside selective Rg1 release, which suppressed macrophage-mediated inflammation. Cel was selectively internalized by FLS through the exposed HAP-1 peptide to inhibit FLS proliferation.Results\n\nIn vitro, HAP@CMR repolarized macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed inflammatory cytokine secretion, and exerted potent inhibitory effects on the proliferation, migration, and invasion of FLS. In a rat collagen-induced arthritis (CIA) model, administration of HAP@CMR led to the most pronounced reduction in paw swelling among all drug-treated groups. Further histological, X-ray, and micro-CT assessments confirmed that this treatment effectively alleviated synovial inflammation, attenuated cartilage erosion, and inhibited bone destruction.Conclusion\n\nThis novel nanoplatform promotes FLS apoptosis while mitigating local inflammatory responses, providing a promising therapeutic strategy for RA.",
  "abstract_shown": true,
  "affiliations": [
    "College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People's Republic of China.",
    "Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, People's Republic of China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yani Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruibo Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Ge Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifei Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyan Hua"
    },
    {
      "affs": [
        0
      ],
      "name": "Bangyun Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuetao Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuanyuan Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Liang Kong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2eb1wm8ccyc16.bib",
  "cited_by": 0,
  "doi": "10.2147/ijn.s644123",
  "fulltext_url": "https://europepmc.org/articles/PMC13718829",
  "id": "2eb1wm8ccyc16",
  "issns": [
    "1176-9114",
    "1178-2013"
  ],
  "landing_url": "https://europepmc.org/article/MED/42960261",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2745|Rheumatoid Arthritis Research and Therapies"
    ]
  ],
  "openalex": "W7223441948",
  "pdf_url": "https://europepmc.org/articles/PMC13718829?pdf=render",
  "pmcid": "PMC13718829",
  "pmid": "42960261",
  "published": "2026-10-25",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/2eb1wm8ccyc16.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:50Z",
      "native_id": "MED:42960261",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960261"
    },
    {
      "first_seen": "2026-11-02T12:22:47Z",
      "native_id": "PMC13718829",
      "source": "pmc",
      "url": "https://doi.org/10.2147/ijn.s644123"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Rheumatoid Arthritis Research and Therapies",
      "subfield": "general"
    }
  ],
  "title": "Microenvironment-Triggered Sequentially Targeted Micelles for Dual Regulation of Macrophages and Fibroblast-Like Synoviocytes via ROS-Responsive Rg1 Release and HAP-1-Mediated Celastrol Delivery in Rheumatoid Arthritis Therapy.",
  "title_text": "Microenvironment-Triggered Sequentially Targeted Micelles for Dual Regulation of Macrophages and Fibroblast-Like Synoviocytes via ROS-Responsive Rg1 Release and HAP-1-Mediated Celastrol Delivery in Rheumatoid Arthritis Therapy.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:47Z",
  "url": "https://research.draconitic.com/paper/2eb1wm8ccyc16",
  "venue": "International journal of nanomedicine",
  "versions": []
}