taribavirin and Liver-Neoplasms

Hepatocellular carcinoma (HCC) is a global health problem with regional differences in epidemiological statistics. Co-assembling the drug nanoparticles and targeting moieties could improve the therapeutic delivery of anti-cancer drugs. In this attempt, we tracked the extrinsic and intrinsic apoptotic pathways in HCC cells using viramidine (VRM)-loaded aptamer (APT) nanoparticles. In these NPs, both APT and VRM act as targeted ligands/drugs to HCC cells. The NPs were characterized using TEM, ESI-MS, FTIR, and

Topics: Apoptosis; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Nanoparticles

Current estimates indicate that hepatocarcinoma is the leading cause of death globally. There is interest in utilizing nanomedicine for cancer therapy to overcome side effects of chemo-interventions. Ribavirin, an antiviral nucleoside inhibitor, accumulates inside red blood cells, causing anemia. Its analog, viramidine, can concentrate within hepatocytes and spare red blood cells, thus limiting anemia. Hepatocarcinoma cells have a large number of asialoglycoprotein receptors on their membranes that can bind galactosyl-terminating solid lipid nanoparticles (Gal-SLN) and internalize them. Here, viramidine, 5-fluorouracil, and paclitaxel-loaded Gal-SLN were characterized inside cells. Cytotoxicities of free-drug, nano-void, and drug-loaded Gal-SLN were evaluated using HepG2 cells; over 3 days, cell viability was measured. To test the mechanistic pathway, we investigated in vitro apoptosis using flow cytometry and in ovo angiogenesis using the CAM assay. Results showed that 1 and 2 μM of the viramidine-encapsulated Gal-SLN had the highest cytotoxic effect, achieving 80% cell death with a steady increase over 3 days, with induction of apoptosis and reduction of necrosis and angiogenesis, compared to free-drugs. Gal-SLN application on breast cancer MCF-7 cells confirmed its specificity against liver cancer HepG2 cells. We conclude that viramidine-encapsulated Gal-SLN has anticancer and anti-angiogenic activities against hepatocarcinoma.

Topics: Angiogenesis Inhibitors; Apoptosis; Breast Neoplasms; Carcinoma, Hepatocellular; Galactose; Hep G2 Cells; Humans; Liver Neoplasms; MCF-7 Cells; Nanoparticles; Neovascularization, Pathologic; Ribavirin

Topics: Antineoplastic Agents; Antiviral Agents; Carcinoma, Hepatocellular; Drug Delivery Systems; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Humans; Liver Neoplasms; Ribavirin; Treatment Outcome