{
  "abstract": "Liver fibrosis is a severe complication of diverse chronic liver diseases characterized by a dysregulated hepatic microenvironment, and effective clinical therapeutic strategies for this condition remain lacking to date. Chimeric antigen receptor macrophages (CAR-Ms) hold considerable therapeutic potential for liver fibrosis via antigen-specific recognition and efferocytotic activity, yet their clinical translation is largely hindered by the sophisticated ex vivo preparation procedures. Herein, we report an in situ CAR-M engineering strategy that uses a phosphatidylserine (PS)-incorporated, macrophage-targeted lipid nanoparticle (LNP) for the codelivery of CAR messenger RNA (mRNA) and Cas9 mRNA in vivo. Our findings demonstrate that this engineered LNP achieves efficient targeting of liver-resident macrophages. Transfection with fibroblast activation protein α (FAPα)-CAR mRNA equips macrophages with the capacity to specifically target activated hepatic stellate cells (aHSCs), whereas Cas9-mediated follistatin-like protein 1 (FSTL-1) gene editing enhances the efferocytotic function of macrophages in liver tissues. Consequently, functional CAR-Ms are generated in situ, which elicits robust antifibrotic effects, including reduced collagen deposition, restored sinusoidal architecture and enhanced immune-mediated antifibrotic activity. Collectively, our customized LNP-mediated in situ engineering of liver macrophages into CAR-Ms enables precise antifibrotic intervention for liver fibrosis and circumvents the cumbersome ex vivo CAR-M preparation process.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Ultrasound, Laboratory of Novel Optoacoustic (Ultrasonic) Imaging, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.",
    "Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.",
    "PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hong Xiao",
      "orcid": "0000-0003-1184-4279"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoxia Li",
      "orcid": "0000-0003-3039-5931"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaimin Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifei Leng"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyan Miao",
      "orcid": "0009-0007-2952-0869"
    },
    {
      "affs": [
        0
      ],
      "name": "Tinghui Yin",
      "orcid": "0000-0003-4201-3953"
    },
    {
      "affs": [
        1
      ],
      "name": "Xintao Shuai",
      "orcid": "0000-0003-4271-0310"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Ren",
      "orcid": "0000-0003-2599-9001"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e1vgjf48s0jk6.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeh6590",
  "fulltext_url": "https://europepmc.org/articles/PMC13693692",
  "id": "e1vgjf48s0jk6",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeh6590",
  "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": [
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7223369261",
  "pdf_url": "https://europepmc.org/articles/PMC13693692?pdf=render",
  "pmcid": "PMC13693692",
  "pmid": "42913010",
  "published": "2026-10-23",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/e1vgjf48s0jk6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeh6590",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeh6590"
    },
    {
      "first_seen": "2026-10-30T12:20:03Z",
      "native_id": "MED:42913010",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42913010"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Interference and Gene Delivery",
      "subfield": "molecular-biology"
    }
  ],
  "title": "In situ CAR-M engineered by liposomal mRNA nanomedicine remodels fibrotic microenvironment for ameliorating liver fibrosis",
  "title_text": "In situ CAR-M engineered by liposomal mRNA nanomedicine remodels fibrotic microenvironment for ameliorating liver fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:03Z",
  "url": "https://research.draconitic.com/paper/e1vgjf48s0jk6",
  "venue": "Science Advances",
  "versions": []
}