Journal
MOLECULES
Volume 27, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/molecules27072082
Keywords
hepatocellular carcinoma; metastasis; ASGPR; gene therapy; VEGF; VEGFR2 signaling pathway
Funding
- National Natural Science Foundation of China [31700706]
- Natural Science Foundation of Jiangsu Province [BK20202002]
- National Key R&D Program of China [2018YFA0901700]
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In this study, a formulation containing 5-FU and siRNA against VEGF/VEGFR signaling pathway was established and delivered through GalNAc-modified nanocarriers, showing significant anti-metastatic activity against hepatocellular carcinoma. This holds great promise for future treatment of metastatic HCC.
Hepatocellular carcinoma (HCC) is a highly malignant tumor related to high mortality and is still lacking a satisfactory cure. Tumor metastasis is currently a major challenge of cancer treatment, which is highly related to angiogenesis. The vascular endothelial growth factor (VEGF)/VEGFR signaling pathway is thus becoming an attractive therapeutic target. Moreover, chemotherapy combined with gene therapy shows great synergistic potential in cancer treatment with the promise of nanomaterials. In this work, a formulation containing 5-FU and siRNA against the VEGF/VEGFR signaling pathway into N-acetyl-galactosamine (GalNAc)-modified nanocarriers is established. The targeting ability, biocompatibility and pH-responsive degradation capacity ensure the efficient transport of therapeutics by the formulation of 5-FU/siRNA@GalNAc-pDMA to HCC cells. The nano-construct integrated with gene/chemotherapy exhibits significant anti-metastatic HCC activity against C5WN1 liver cancer cells with tumorigenicity and pulmonary metastasis in the C5WN1-induced tumor-bearing mouse model with a tumor inhibition rate of 96%, which is promising for future metastatic HCC treatment.
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