Heterogeneous Magnetic Resonance Nanoprobe for Assisting Liver Fibrosis Three-Dimensional Reconstruction and Cascaded Therapy.

Liver fibrosis is a chronic, progressive liver disease that can lead to irreversible cirrhosis and hepatocellular carcinoma. However, the early and accurate diagnosis of liver fibrosis remains a dilemma in clinical research. In this study, a gadolinium-palladium nanocluster with decapeptide (L10) and glucose oxidase (GOx) grafting (GPPGL) was developed for accurate liver fibrosis staging and synergistic antifibrotic therapy. L10, with a strong affinity for Collagen I, can mediate this nanoplatform to target the liver fibrosis region, enabling it to achieve enhanced accumulation in the liver. Therefore, GPPGL, with magnetic resonance imaging (MRI) contrast enhancement capacity, can accurately grade liver fibrosis to different degrees. Then, three-dimensional reconstruction and histogram-based features of MRI images are further conducted to quantitatively and qualitatively analyze the degree of liver fibrosis. GOx, with strong glucose consumption, can enhance the catalase- and peroxidase-like activities of the nanoplatform in a cascade. Systemic delivery of GPPGL can synergistically inhibit the activation of hepatic stellate cells and reduce their collagen production by alleviating liver fibrosis hypoxia, inducing ferroptosis, and achieving starvation therapy. No significant side effects during both histological and hematological examinations were observed. Therefore, GPPGL has promising prospects for achieving accurate liver fibrosis staging and synergistic antifibrotic therapy.