Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;52(1):48-61.
doi: 10.1007/s00259-024-06894-5. Epub 2024 Sep 5.

Non-invasive diagnosis of liver fibrosis via MRI using targeted gadolinium-based nanoparticles

Shiman Wu #  1   2   3 , Tingting Xu #  4 , Jiahao Gao #  1 , Qi Zhang  1 , Yuxin Huang  1 , Zonglin Liu  1 , Xiaozhu Hao  1 , Zhenwei Yao  1 , Xing Hao  5 , Pu-Yeh Wu  6 , Yue Wu  7 , Bo Yin  8 , Zhongmin Tang  9
Affiliations

Non-invasive diagnosis of liver fibrosis via MRI using targeted gadolinium-based nanoparticles

Shiman Wu et al. Eur J Nucl Med Mol Imaging. 2024 Dec.

Abstract

Introduction: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI).

Materials and methods: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner.

Results: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice.

Conclusions: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.

Keywords: Gadolinium; Hyaluronic acid; Liver fibrosis; MRI; Nanoprobes.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval: All animal experiments were conducted in accordance with institutional guidelines and approved by the institutional animal ethics committee (approval number: 2023-HSYY-533GZS). The Institutional Review Board of Huashan Hospital approved the use of human samples for this study (approval number: 2021-HSYY-029). Competing interests: The authors declare no conflicts of interest.

Similar articles

See all similar articles

Cited by

References

    1. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14:397–411. https://doi.org/10.1038/nrgastro.2017.38 . - DOI - PubMed
    1. Kurniawan DW, Jajoriya AK, Dhawan G, Mishra D, Argemi J, Bataller R, et al. Therapeutic inhibition of spleen tyrosine kinase in inflammatory macrophages using PLGA nanoparticles for the treatment of non-alcoholic steatohepatitis. J Control Release. 2018;288:227–38. https://doi.org/10.1016/j.jconrel.2018.09.004 . - DOI - PubMed
    1. Zhao X, Amevor FK, Xue X, Wang C, Cui Z, Dai S, et al. Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: a comprehensive review. J Nanobiotechnol. 2023;21:121. https://doi.org/10.1186/s12951-023-01876-5 . - DOI
    1. Muns JA, Schooten E, van Dasselaar RDJ, Noordman YE, Adamzek K, Eibergen AC, et al. Preclinical targeting of liver fibrosis with a 89Zr-labeled Fibrobody® directed against platelet derived growth factor receptor-β. Eur J Nucl Med Mol Imaging. 2024. https://doi.org/10.1007/s00259-024-06785-9 . - DOI - PubMed - PMC
    1. Xue LY, Jiang ZY, Fu TT, Wang QM, Zhu YL, Dai M, et al. Transfer learning radiomics based on multimodal ultrasound imaging for staging liver fibrosis. Eur Radiol. 2020;30:2973–83. https://doi.org/10.1007/s00330-019-06595-w . - DOI - PubMed - PMC

LinkOut - more resources