肝纤维化是多种慢性肝损伤的共同病理改变，可发展成肝硬化，甚至肝癌。肝星状细胞（HSCs）的活化是肝纤维化发生发展的中心环节，抑制此过程可有效抑制肝纤维化。因HSCs活化受多方面影响，且不同通路间有相互作用，所以单独抑制某个通路并不能充分抑制此过程。因此，通过共给药从多方面同时抑制HSCs的激活是治疗肝纤维化的有效手段。为了进一步提高药效，基于HSCs表面高表达介导维生素A特异性摄取的视黄醇结合蛋白受体（RBPR），我们构建了一种新型靶向递药系统（Vit A-Lipo）。首先制备Vit A-Lipo，包载具有不同作用机制的抗肝纤维化药物水飞蓟宾和环巴胺，并靶向传递至HSCs，以期实现肝纤维化的有效治疗。预实验表明，Vit A-Lipo确能增加HSCs对药物的摄取，这为本课题后期对载药Vit A-Lipo的抗纤维化作用和机制研究等工作奠定了基础。本项目的开展对肝纤维化的有效治疗具有重要意义。

Hepatic fibrosis is a common pathological change of various chronic liver injury, which could develop into liver cirrhosis or even liver cancer. The activation of hepatic stellate cells (HSCs) is critical in hepatic fibrosis formation and progression, and inhibiting this process can inhibit liver fibrosis effectively. On account of the activation of HSCs is regulated by many factors and interaction exists between them, the inhibition of one pathway alone could not fully suppress HSCs activation. Therefore, co-delivery of drugs which could suppressing HSCs activation through different mechanisms is an effective method for liver fibrosis therapy. In order to further improve the efficacy, we proposed to construct a novel targeted drug delivery system (DDS) based on retinol binding protein receptor (RBPR) which is highly expressed on the surface of HSCs and mediates vitamin A specific uptake by HSCs. According to related literature, silibinin and cyclopamine are expected to inhibit HSCs activation by synergistic effect. In this study, they will be loaded into liposome firstly, which will be then decorated with vitamin A on its surface. This DDS could deliver drugs to HSCs targetedly, contributing to potent therapy for liver fibrosis. Preliminary experiments showed that vitamin A modified targeted liposome could increase drug intake by HSCs significantly, laiding a solid foundation for further study of this project, such as the anti-fibrotic effect and its mechanism in vitro and in vivo. In conclusion, this project is of great significance for effective hepatic fibrosis therapy.