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

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). NaGdF${}_4$ nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF${}_4$@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF${}_4$@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 NaGdF${}_4$@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. NaGdF${}_4$@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM${}^{-1}$ s${}^{-1}$). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF${}_4$@PEG@HA nanoprobes by JS1 cells compared to NaGdF${}_4$@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF${}_4$@PEG@HA. NaGdF${}_4$@PEG@HA demonstrated higher targeting ability in fibrotic mice. NaGdF${}_4$@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.