The effectiveness of chemotherapy in hepatocellular carcinoma (HCC) is restricted by chemo-resistance and systemic side effects. To improve the efficacy and safety of chemotherapeutics in HCC ...management, scientists have attempted to deliver these drugs to malignant tissues using targeted carriers as nanoparticles (NPs). Among the three types of NPs targeting (active, passive, and stimuli-responsive), active targeting is the most commonly investigated in HCC treatment. Despite the observed promising results so far, clinical research on nanomedicine targeting for HCC treatment still faces many challenges.These include batch-to-batch physicochemical properties' variations, limiting large scale production and insufficient data on human and environmental toxicities. This review summarized the characteristics of different nanocarriers, ligands, targeted receptors on HCC cells and provided recommendations to overcome the challenges, facing this novel line of treatment for HCC.
