Abstract
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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
National Key R&D Program of China
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Cited by
3 articles.
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