TFRC and cancer: Thus, the overexpression or specific expression of corresponding binding ligands at the cancer cell surface endow active targeting capabilities of these ligand-modifying systems to cancer cells with over-expressed folic acid receptor [23], specific antigen [24], epidermal growth factor receptor [25, 26], transferrin receptor [27], etc. However, due to the biological barriers and protein corona, the engineered active-targeting DDSs may be cleared by the system established by Kupffer cells, liver sinusoidal endothelial cells, stellate cells and hepatic cells [28].