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A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis

Author

Listed:
  • Jiahao Gao

    (Fudan University
    Fudan University)

  • Ya Wang

    (Fudan University)

  • Xianfu Meng

    (Fudan University
    Navy Medical University)

  • Xiaoshuang Wang

    (Fudan University)

  • Fang Han

    (Fudan University)

  • Hao Xing

    (Fudan University)

  • Guanglei Lv

    (Yiwu Research Institute of Fudan University)

  • Li Zhang

    (Tongji University School of Medicine)

  • Shiman Wu

    (Fudan University)

  • Xingwu Jiang

    (Fudan University)

  • Zhenwei Yao

    (Fudan University)

  • Xiangming Fang

    (Nanjing Medical University)

  • Jiawen Zhang

    (Fudan University)

  • Wenbo Bu

    (Fudan University
    Fudan University)

Abstract

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients’ samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

Suggested Citation

  • Jiahao Gao & Ya Wang & Xianfu Meng & Xiaoshuang Wang & Fang Han & Hao Xing & Guanglei Lv & Li Zhang & Shiman Wu & Xingwu Jiang & Zhenwei Yao & Xiangming Fang & Jiawen Zhang & Wenbo Bu, 2024. "A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52308-3
    DOI: 10.1038/s41467-024-52308-3
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    References listed on IDEAS

    as
    1. Neil C. Henderson & Florian Rieder & Thomas A. Wynn, 2020. "Fibrosis: from mechanisms to medicines," Nature, Nature, vol. 587(7835), pages 555-566, November.
    2. Jérôme Boursier & Marine Roux & Charlotte Costentin & Julien Chaigneau & Céline Fournier-Poizat & Aldo Trylesinski & Clémence M. Canivet & Sophie Michalak & Brigitte Bail & Valérie Paradis & Pierre Be, 2023. "Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Mani Salarian & Ravi Chakra Turaga & Shenghui Xue & Maysam Nezafati & Khan Hekmatyar & Jingjuan Qiao & Yinwei Zhang & Shanshan Tan & Oluwatosin Y. Ibhagui & Yan Hai & Jibiao Li & Rao Mukkavilli & Malv, 2019. "Early detection and staging of chronic liver diseases with a protein MRI contrast agent," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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