Frontiers in Pharmacology (Sep 2022)

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

  • Jingliang Wu,
  • Cuiping Qi,
  • Cuiping Qi,
  • Hao Wang,
  • Qing Wang,
  • Jingui Sun,
  • Jinping Dong,
  • Guohua Yu,
  • Zhiqin Gao,
  • Bo Zhang,
  • Guixiang Tian

DOI
https://doi.org/10.3389/fphar.2022.961788
Journal volume & issue
Vol. 13

Abstract

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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.

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