Hepatotropic Nanomedicine and Targeted Nanocarriers for Liver Diseases and Hepatocellular Carcinoma.

Despite the continuous increase in number of patients with liver diseases, including cirrhosis, fibrosis, viral hepatitis, Metabolic dysfunction-associated steatotic liver disease (MASLD), Metabolic dysfunction-associated steatohepatitis (MASH), and hepatocellular carcinoma (HCC), conventional drug delivery systems often fail to meet treatment requirements due to low bioavailability, poor water solubility, rapid metabolism in the liver, and dose limitations due to their systemic toxicity. The use of hepatotropic nanomedicine could provide a viable solution by developing drugs and drug-delivery systems in accordance with specific properties of the liver, including its cellular diversity and molecular characteristics related to the development of the particular disease. The current review describes various liver-targeted nanocarriers that take advantage of receptor-mediated uptake, fenestrated sinusoidal endothelium, and some characteristics of the tumor microenvironment, such as acidity, oxidative stress, and overexpression of certain enzymes. The review covers different polymeric, lipid, inorganic, biomimetic, and nucleic acid-based systems with both passive and active approaches for targeting hepatocytes, Kupffer cells, hepatic stellate cells, and HCC cells.