Preparation and Antitumor Activity Evaluation of Dual-Targeted Liposomes Functionalized with SP94 and BR2 Peptides for Hepatocellular Carcinoma

In this study, we developed a multifunctional nanodelivery system to achieve precise treatment of hepatocellular carcinoma (HCC). Previous work by our group synthesized a matrine derivative A6, which exhibits potent antitumor activity; however, its further development and application have been limited by issues such as poor solubility and stability. Meanwhile, the clinical use of the chemotherapeutic agent doxorubicin (DOX) is restricted by its cardiotoxicity. To address these challenges, we designed a dual-drug-loaded liposomal system (SP94/BR2–A6/DOX–LP) that encapsulates both A6 and DOX, demonstrating high drug loading capacity and encapsulation efficiency. Furthermore, by functionalizing the liposome surface with SP94 and BR2 peptides enhanced tumor their targeting and therapeutic efficacy. Our findings indicate that A6 and DOX act synergistically against HCC. The dual-targeting strategy mediated by SP94 and BR2 promotes precise accumulation of the liposomes in hepatocellular carcinoma cells, significantly improving antitumor outcomes. This multifunctional nanodelivery system significantly enhances both the targeting efficiency and therapeutic efficacy of the loaded drugs, thereby paving the way for a promising new strategy in the precision treatment of hepatocellular carcinoma.