Targeted Nanocomplex Delivery for Protecting Vascular Integrity and Enhancing Anticancer Effects in Hepatocellular Carcinoma

In cancer treatment, it is critical to enhance drug delivery efficiency to the target area while minimizing the side effects of chemotherapeutic drugs. Although intravenous administration of anticancer agents is commonly used, it often results in blood vessel damage and systemic side effects as well as poor targeted delivery. Therefore, developing new drug delivery formulations is essential to improve anticancer efficacy while reducing side effects. Herein, a nanohybrid methodology is presented to improve the targeted delivery of doxorubicin (DOX) for treating hepatocellular carcinoma (HCC) and to minimize vascular damage. An albumin–glucosamine (AG) lipid complex (LC), composed of stearyl glycyrrhetinate (SG) and DSPE‐PEG, is designed to serve as a liver cancer‐specific delivery system. The nanohybrid formulation, SGLC/DOX@AG, demonstrates significant anticancer activity and reduced side effects, as demonstrated by in vitro, in vivo, and cancer‐on‐a‐chip models. This study presents a novel carrier design and application model for drug formulation development and efficacy validation, providing insights into therapeutic development for HCC.