Department of Radiology, Huashan hospital, Fudan University, 200040, Shanghai, P. R. China.
Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, P. R. China.
Eur J Nucl Med Mol Imaging. 2024 Dec;52(1):48-61. doi: 10.1007/s00259-024-06894-5. Epub 2024 Sep 5.
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 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF@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@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@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 NaGdF@PEG@HA nanoprobes by JS1 cells compared to NaGdF@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF@PEG@HA. NaGdF@PEG@HA demonstrated higher targeting ability in fibrotic mice.
NaGdF@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.
准确诊断肝纤维化对于预防肝硬化和肝癌至关重要。肝纤维化是由活化的肝星状细胞（HSCs）驱动的，其 CD44 表达水平升高。我们开发了透明质酸（HA）包覆的基于钆的纳米探针，通过 T1 加权磁共振成像（MRI）特异性靶向 CD44 来诊断肝纤维化。
通过热分解合成 NaGdF 纳米颗粒（NPs），并用聚乙二醇（PEG）进行修饰，得到非靶向性 NaGdF@PEG NPs。随后，它们被 HA 包覆，以靶向 HSCs，从而得到靶向肝纤维化的 NaGdF@PEG@HA 纳米探针。特性分析包括透射电子显微镜和 X 射线衍射。使用细胞计数试剂盒-8（CCK-8）评估细胞活力。通过流式细胞术和共聚焦激光扫描显微镜（CLSM）观察到 NaGdF@PEG@HA 纳米探针通过配体-受体相互作用被小鼠 HSCs JS1 细胞内化。使用甲硫氨酸-胆碱缺乏（MCD）饮食诱导 C57BL/6 小鼠肝纤维化。使用 GE Discovery 3.0T MR 750 扫描仪分析 MRI 性能和纳米探针在纤维化和正常肝脏中的分布。
NaGdF@PEG@HA 纳米探针表现出均匀的形态、低毒性和高 T1 弛豫率（7.645 mM⁻¹s⁻¹）。CLSM 和流式细胞术显示，与 NaGdF@PEG 相比，JS1 细胞对 NaGdF@PEG@HA 纳米探针的吞噬作用更强。MRI 扫描显示，注射 NaGdF@PEG@HA 后，纤维化肝脏的 T1 信号高于正常肝脏。NaGdF@PEG@HA 在纤维化小鼠中表现出更高的靶向能力。
NaGdF@PEG@HA 纳米探针能有效靶向 HSCs，具有高 T1 弛豫率，有助于肝纤维化的高效 MRI 诊断。
