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Viramidine-Loaded Galactosylated Nanoparticles Induce Hepatic Cancer Cell Apoptosis and Inhibit Angiogenesis

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Abstract

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.

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Acknowledgments

This manuscript was extracted from the project entitled, “Nano-Drug Delivery for Cancer Therapy” by A.A.A. through the international exchange program at Albany College of Pharmacy and Health Sciences (ACPHS) in collaboration with and funded by the Pharmaceutical Research Institute at ACPHS.

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Authors and Affiliations

  1. Hormones Department, Medical Research Division, National Research Centre, Giza, 12622, Egypt

    Ahmed A. Abd-Rabou

  2. Stem Cell Laboratory, Center of Excellence for Advanced Science, National Research Centre, Giza, 12622, Egypt

    Ahmed A. Abd-Rabou

  3. The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY, 12144, USA

    Dhruba J. Bharali & Shaker A. Mousa

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  1. Ahmed A. Abd-Rabou
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Correspondence to Shaker A. Mousa.

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S.A.M. owns stock in NanoPharmaceuticals LLC, a pharmaceutical company that is developing nano drugs. All the other authors declare that they have no conflicts of interest.

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Abd-Rabou, A.A., Bharali, D.J. & Mousa, S.A. Viramidine-Loaded Galactosylated Nanoparticles Induce Hepatic Cancer Cell Apoptosis and Inhibit Angiogenesis. Appl Biochem Biotechnol 190, 305–324 (2020). https://doi.org/10.1007/s12010-019-03090-2

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