Hepatocellular carcinoma (HCC) is inflammation-related cancer. Persistent inflammatory injury of the liver is an important factor mediating the occurrence and development of liver cancer. Hepatic macrophages play an important role in the inflammatory microenvironment, which mediates tumor immune escape, tumor growth, and metastasis. Previous studies have suggested that L-3,5,3-triiodothyronine (T3) can regulate inflammation; however, its use is associated with serious cardiac side effects, and its role in hepatocarcinogenesis remains unclear. In this study, we aimed to develop an effective T3 delivery system with reduced cardiac toxicity and to explore its effects on HCC occurrence.
T3 liposomes (T3-lipo) were prepared using the thin-film hydration method, and their characteristics, including particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading, drug release, and stability, were evaluated
Compared with T3, T3-lipo had an enhanced inhibitory effect on hepatocarcinogenesis and reduced cardiac side effects in DEN-induced primary HCC in rats. Mechanistically, T3-lipo were absorbed by hepatic macrophages and regulated the secretion of inflammatory cytokines in macrophages by inhibiting inflammatory signaling pathways.
T3-lipo may suppress hepatocarcinogenesis by regulating the inflammatory microenvironment in the liver and reduce the cardiac side effects meanwhile.