Abstract
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(1)- or T(2)-weighted imaging struggles to capture these early-stage lesions. To address this challenge, a highly sensitive and targeted T(1)-T(2) 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(2)/r(1) = 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(1) and T(2) 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.