Li Zehua, Zhang Tongwei, Tao Tongxiang, Liu Yaxuan, Xia Haining, Rehman Sajid Ur, Guo Zeyong, Zhang Jing, Chen Ruiguo, Zhang Zhan, Wang Junfeng, Ma Kun
High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, P. R. China.
University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China.
Adv Sci (Weinh). 2025 Jun;12(23):e2413788. doi: 10.1002/advs.202413788. Epub 2025 Mar 7.
Non-alcoholic fatty liver disease (NAFLD)-induced early-stage liver fibrosis is increasingly common. Non-invasive MRI detection offers an important diagnostic method to prevent fibrosis from progressing to cirrhosis or hepatocellular carcinoma. However, because fibrosis is confined to the periportal areas, and changes in tissue structure and stiffness are minimal, standard T- or T-weighted imaging struggles to capture these early-stage lesions. To address this challenge, a highly sensitive and targeted T-T dual-mode magnetic resonance imaging (MRI) nanoprobe is designed and developed, specifically targeting early-stage liver fibrosis characterized by the activation of hepatic stellate cells (HSCs) and the overexpression of platelet-derived growth factor receptor β (PDGFRβ). The nanoprobe exhibits excellent relaxivity (r/r = 10.7) and precise targeting due to PDGFRβ-specific peptides conjugated to its protein nanocage. In vivo, imaging in animal models demonstrate effective accumulation of the probe in fibrotic regions as NAFLD progressed, with fluorescence signal intensity accurately reflecting the severity of liver fibrosis. Using a 7T MRI system, T and T images are overlaid within 1 h, accurately locating fibrotic areas and improving diagnostic speed and precision. The nanoprobe shows excellent biocompatibility and enhances early fibrosis detection in NAFLD, offering significant clinical potential for early diagnosis, prognosis, and recurrence monitoring.
非酒精性脂肪性肝病(NAFLD)引起的早期肝纤维化日益常见。非侵入性磁共振成像(MRI)检测为预防纤维化进展为肝硬化或肝细胞癌提供了一种重要的诊断方法。然而,由于纤维化局限于门周区域,组织结构和硬度变化极小,标准的T加权或T加权成像难以捕捉这些早期病变。为应对这一挑战,设计并开发了一种高灵敏度、靶向性的T-T双模磁共振成像(MRI)纳米探针,专门针对以肝星状细胞(HSCs)激活和血小板衍生生长因子受体β(PDGFRβ)过表达为特征的早期肝纤维化。该纳米探针由于其蛋白质纳米笼偶联了PDGFRβ特异性肽,表现出优异的弛豫率(r/r = 10.7)和精确的靶向性。在体内,动物模型成像显示随着NAFLD的进展,探针在纤维化区域有效积累,荧光信号强度准确反映肝纤维化的严重程度。使用7T MRI系统,T图像和T图像在1小时内叠加,准确定位纤维化区域,提高诊断速度和精度。该纳米探针具有优异的生物相容性,可增强NAFLD早期纤维化的检测,为早期诊断、预后和复发监测提供了巨大的临床潜力。
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