Engineered Gadolinium-Decorated Magnetic Resonance Nanoprobes for Enhanced Liver Fibrosis Theranostics.

Abstract

Liver fibrosis has the potential to advance to irreversible cirrhosis or hepatocellular carcinoma, rendering early diagnosis and intervention of utmost importance. During liver fibrogenesis, lysyl oxidase enzymes become upregulated, which facilitate ε amino groups of lysine in extracellular matrix proteins to become oxidized, yielding the aldehyde-containing allysine (Lys^Ald). In this context, a novel hydrazine-functionalized gadolinium-platinum nanoplatform (Pt@Gd₂O₃-PEG-N₂H₄) has been engineered to facilitate accurate diagnosis and therapy of liver fibrosis. The platform achieves targeted delivery to activated hepatic stellate cells (aHSCs) via hydrazine-mediated covalent binding to Lys^Ald, which is enriched in fibrotic regions of the liver. Additionally, GPPN exhibits dual enzymatic activities analogous to catalase and peroxidase, providing oxygen to mitigate hypoxia in fibrotic liver tissues and generating highly toxic hydroxyl radicals (·OH) for the selective ablation of aHSCs. There are no significant adverse effects in histological or hematological evaluations. Moreover, GPPN improves magnetic resonance imaging (MRI) signals of liver fibrosis to enable more accurate assessment of disease progression. Overall, GPPN presents considerable potential for the precise diagnosis and effective therapy of liver fibrosis.