Nano-encapsulation of drugs to target hepatic stellate cells: Toward precision treatments of liver fibrosis

Liver fibrosis is characterized by excessive extracellular matrix (ECM) deposition triggered by hepatic stellate cells (HSCs). As central players in fibrosis progression, HSCs are the most important therapeutic targets for antifibrotic therapy. However, owing to the limitations of systemic drug administration, there is still no suitable and effective clinical treatment. In recent years, nanosystems have demonstrated expansive therapeutic potential and evolved into a clinical modality. In liver fibrosis, nanosystems have undergone a paradigm shift from targeting the whole liver to locally targeted modifying processes. Nanomedicine delivered to HSCs has significant potential in managing liver fibrosis, where optimal management would benefit from targeted delivery, personalized therapy based on the specific site of interest, and minor side effects. In this review, we present a brief overview of the role of HSCs in the pathogenesis of liver fibrosis, summarize the different types of nanocarriers and their specific delivery applications in liver fibrosis, and highlight the biological barriers associated with the use of nanosystems to target HSCs and approaches available to solve this issue. We further discuss in-depth all the molecular target receptors overexpressed during HSC activation in liver fibrosis and their corresponding ligands that have been used for drug or gene delivery targeting HSCs.