International Journal of Nanomedicine (Jun 2022)

GA&HA-Modified Liposomes for Co-Delivery of Aprepitant and Curcumin to Inhibit Drug-Resistance and Metastasis of Hepatocellular Carcinoma

  • Li Y,
  • Wu J,
  • Lu Q,
  • Liu X,
  • Wen J,
  • Qi X,
  • Liu J,
  • Lian B,
  • Zhang B,
  • Sun H,
  • Tian G

Journal volume & issue
Vol. Volume 17
pp. 2559 – 2575

Abstract

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Yanying Li,1,2 Jingliang Wu,2 Qiao Lu,1 Xuemin Liu,2 Jiaxuan Wen,3 Xiaohui Qi,1 Jianhao Liu,4 Bo Lian,1 Bo Zhang,4 Hengyi Sun,1 Guixiang Tian1 1School of Life Science and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2School of Nursing, Weifang University of Science and Technology, Weifang, 262700, People’s Republic of China; 3School of Nursing, Weifang Medical University, Weifang, 261053, People’s Republic of China; 4School of Pharmacy, Weifang Medical University, Weifang, 261053, People’s Republic of ChinaCorrespondence: Hengyi Sun; Guixiang Tian, Email [email protected]; [email protected]: Tumor microenvironment (TME) plays a vital role in the development of hepatocellular carcinoma (HCC). Mounting evidence indicates that peripheral nerves could induce a shift from quiescent hepatic stellate cells (HSCs) to cancer-associated fibroblasts (CAFs) by secreting substance P (SP). The anti-tumor strategy by targeting “SP-HSCs-HCC” axis might be an effective therapy to inhibit tumor growth and metastasis.Objective: In this study, we prepared novel liposomes (CUR-APR/HA&GA-LPs) modified with hyaluronic acid (HA) and glycyrrhetinic acid (GA) for co-delivery aprepitant (APR) and curcumin (CUR), in which APR was chosen to inhibit the activation of HSCs by blocking SP/neurokinin-1 receptor (NK-1R), and CUR was used to induce apoptosis of tumor cells.Results: To mimic the TME, we established “SP+HSCs+HCC” co-cultured cell model in vitro. The results showed that CUR-APR/HA&GA-LPs could be taken up by CAFs and HCC simultaneously, and inhibit tumor cell migration. Meanwhile, the “SP+m-HSCs+HCC” co-implanted mice model was established to evaluate the anti-tumor effect in vivo. The results showed that CUR-APR/HA&GA-LPs could inhibit tumor proliferation and metastasis, and reduce extracellular matrix (ECM) deposition and tumor angiogenesis, indicating a superior anti-HCC effect.Conclusion: Overall, the combination therapy based on HA&GA-LPs could be a potential nano-sized formulation for anti-HCC therapy.Keywords: hepatocellular carcinoma, hepatic stellate cells, substance P, liposomes, co-delivery

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