IGFIIR Aptamer-Functionalized Liposomes for Targeted Delivery of Sorafenib to Ameliorate Liver Fibrosis

Abstract

Liver fibrosis, a major cause of morbidity in chronic liver diseases, lacks effective therapies. Activated hepatic stellate cells (HSCs) are a promising therapeutic target for liver fibrosis, as their transformation into myofibroblasts drives disease progression by excessively depositing an extracellular matrix. Despite its antifibrotic potential, sorafenib faces clinical challenges due to poor aqueous solubility and lack of HSC specificity. To overcome these challenges, we developed IGFIIR aptamer-functionalized liposomes loaded with sorafenib (Apt-Lipo-SF), aiming to facilitate targeted delivery of sorafenib to activated HSCs with the aid of the IGFIIR aptamer and to augment its antifibrotic efficacy. Our findings demonstrated that the aptamer-functionalized liposomes exhibited enhanced cellular uptake in LX-2 cells and Apt-Lipo-SF could effectively suppress HSC activation, with its antifibrotic efficacy superior to that of free sorafenib. Apt-Lipo-SF developed in this study significantly enhanced the antifibrotic effect through targeted delivery, providing a new strategy for the treatment of liver fibrosis.