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GA&HA-Modified Liposomes for Co-Delivery of Aprepitant and Curcumin to Inhibit Drug-Resistance and Metastasis of Hepatocellular Carcinoma
BACKGROUND: 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)...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188407/ https://www.ncbi.nlm.nih.gov/pubmed/35698562 http://dx.doi.org/10.2147/IJN.S366180 |
Sumario: | BACKGROUND: 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. |
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