Hepatocellular Carcinoma-Targeted Icariside II Nanomicelles: Engineering a Glycyrrhetinic Acid-Modified Copolymer Platform for Enhanced Tumor Therapy

Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide, accounting for about 90% of all primary liver malignancies. The emergence of natural antitumor compounds provides a new strategy for the treatment of HCC, but their delivery <i>in vivo</i> has become a major problem. In this study, the copolymer of the natural product glycyrrhetinic acid (AMGA) was prepared and served as a carrier for encapsulation of the natural active ingredient Icariside II (AMGA@ICAII). The results show that AMGA still retains the interaction with GA-R and achieves active targeting by interacting with GA-R. In addition, GA-modification changes the physical chemistry nature of the carrier, providing it with better colloidal stability. AMGA@ICAII significantly inhibited the proliferation of the human hepatoma cell line HepG-2 <i>in vitro</i> compared with other treatment groups. Furthermore, AMGA@ICAII improved the distribution of ICAII in the C57BL/6J mouse Hepa1-6 hepatoma model and showed a significant antitumor effect. This work demonstrated that small molecule target modification in the hydrophobic segment of block copolymer will do benefit to improve the performance of the carrier, while retaining ligand-receptor-mediated targeting properties and providing a reference for the targeted delivery of anticancer agents.