Mixed Nanoscale Liposomes Co-Encapsulating Curcumin and Berberine Inhibit Activated Hepatic Stellate Cell-Induced Drug Resistance and Tumor Metastasis

The combination therapy based on nanoscale materials has been proven an effective approach for cancer treatment. In this study, berberine (BBR) and curcumin (CUR) were loaded into mixed liposomes (CUR-GL/BBR-HL). To simulate a tumor microenvironment (TME), the dual-cell research model (SMMC7721 + LX-2) and orthotopic tumor-bearing mice model were established for antiproliferation and antimetastasis evaluation. The results showed that the mixed liposomes exhibited strong cytotoxicity and antimigration effect against the dual-cell research model. Notably, CUR-GL/BBR-HL effectively inhibited the activation of hepatic stellate cells (HSCs), extracellular matrix deposition, and tumor angiogenesis in vivo, resulting in an enhanced anticancer effect. The anti-HCC mechanism revealed that CUR-GL/BBR-HL could inhibit drug resistance and the metastasis of tumor cells by downregulating the expression of P-gp and vimentin, respectively. Hence, the combined therapeutic strategy could effectively inhibit cancer growth, and CUR-GL/BBR-HL might be a potential formulation for anticancer therapy.