Curcumin and berberine co-loaded liposomes for anti-hepatocellular carcinoma therapy by blocking the cross-talk between hepatic stellate cells and tumor cells

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment (TME). In hepatocellular carcinoma (HCC), quiescent hepatic stellate cells (HSCs) could be activated to become CAFs, which play a critical role in tumor progression and drug resistance. Therefore, recent efforts have been focused on combining anti-HSC and pro-apoptotic activities to improve anti-tumor efficacy of drugs. In this study, glycyrrhetinic acid and hyaluronic acid-modified liposomes (GA-HA-Lip) were prepared for co-delivery of curcumin (CUR) and berberine (BBR) for the treatment of HCC. Furthermore, we established the LX-2+BEL-7402 co-cultured cell model and implanted the m-HSCs+H22 cells into a mouse to evaluate the anti-tumor effect of CUR & BBR/GA-HA-Lip both in vitro and in vivo. The results showed that CUR & BBR/GA-HA-Lip could accumulate in tumor tissues and be taken up by HSCs and BEL-7402 cells simultaneously. Compared with free CUR, the combination therapy based on GA-HA-Lip exhibits stronger pro-apoptotic and anti-proliferation effect both in vitro and in vivo. The anti-tumor mechanistic study revealed that CUR & BBR/GA-HA-Lip could inhibit the activation of HSCs and restrain drug resistance of tumor cells. In summary, CUR & BBR/GA-HA-Lip could be a promising nano-sized formulation for anti-tumor therapy.

Automated summary

In this study, glycyrrhetinic acid and hyaluronic acid-modified liposomes were prepared for co-delivery of curcumin and berberine for the treatment of hepatocellular carcinoma. The results showed that the liposomes could accumulate in tumor tissues and be taken up by relevant cells simultaneously. They exhibited stronger pro-apoptotic and anti-proliferation effect compared to free curcumin, and could inhibit the activation of hepatic stellate cells and restrain drug resistance of tumor cells.