Liver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications

Hepatocytes exert pivotal roles in metabolism, protein synthesis and detoxification. Non-parenchymal liver cells (NPCs), largely comprising macrophages, dendritic cells, hepatic stellate cells and liver sinusoidal cells (LSECs), serve to induce immunological tolerance. Therefore, the liver is an important target for therapeutic approaches, in case of both (inflammatory) metabolic diseases and immunological disorders. This review aims to summarize current preclinical nanodrug-based approaches for the treatment of liver disorders. So far, nano-vaccines that aim to induce hepatitis virus-specific immune responses and nanoformulated adjuvants to overcome the default tolerogenic state of liver NPCs for the treatment of chronic hepatitis have been tested. Moreover, liver cancer may be treated using nanodrugs which specifically target and kill tumor cells. Alternatively, nanodrugs may target and reprogram or deplete immunosuppressive cells of the tumor microenvironment, such as tumor-associated macrophages. Here, combination therapies have been demonstrated to yield synergistic effects. In the case of autoimmune hepatitis and other inflammatory liver diseases, anti-inflammatory agents can be encapsulated into nanoparticles to dampen inflammatory processes specifically in the liver. Finally, the tolerance-promoting activity especially of LSECs has been exploited to induce antigen-specific tolerance for the treatment of allergic and autoimmune diseases.

Automated summary

Hepatocytes play important roles in metabolism, protein synthesis, and detoxification, while non-parenchymal liver cells induce immunological tolerance. This review summarizes the current preclinical nanodrug-based approaches for the treatment of liver disorders, including targeting hepatitis virus-specific immune responses, treating chronic hepatitis with nanoformulated adjuvants, and using nanodrugs to target and kill liver cancer cells. It also discusses the use of nanodrugs to reprogram or deplete immunosuppressive cells in the tumor microenvironment and encapsulate anti-inflammatory agents for the treatment of autoimmune hepatitis and other inflammatory liver diseases. Additionally, the tolerance-promoting activity of liver sinusoidal cells is exploited for the treatment of allergic and autoimmune diseases.