Abstract
Nanotechnology has become a promising approach for addressing cancer therapy limitations because it reduces side effects and increases the efficacy of antineoplastic agents. Therefore, this research was designed to compare the in vitro therapeutic efficacy and in vivo adverse effects of gemcitabine (GEM) and gemcitabine-loaded silver nanoparticles (GEM-AgNPs). GEM molecules were successfully attached to AgNP surfaces with a homogenous and spherical shape. The zeta size of AgNPs and GEM-AgNPs was 79.35 ± 3.2 and 75.1 ± 7 nm, respectively. The anticancer effect of AgNPs and GEM-AgNPs was investigated against a human hepatocellular carcinoma cell line (HepG2), and cytotoxic activity was evaluated by MTT assay. Apoptosis/necrosis and cell cycle arrest were also assessed. The cytotoxic activity was recorded in a concentration-dependent way. The findings have shown that GEM-AgNPs induced a better cytotoxic effect with an IC50 value of 13.63 μg/mL compared to GEM (IC50 value of 24.19 μg/mL) or AgNPs alone (IC50 value of 50.6 μg/mL). GEM-AgNPs induced pre-G1 arrest and apoptotic/necrotic cell death. Our in vivo analysis involved the use of 40 male rats assigned equally into the control rats, and rats injected intraperitoneally with GEM (134 mg/kg), AgNPs (1 mg/kg), and GEM-AgNPs (134 mg/kg). GEM and GEM-AgNPs were administered on the 1st, 7th, and 14th day of the experiment. Intraperitoneal GEM injection induced marked hematological, biochemical, hepatorenal, and histopathological alterations, while the loading of GEM in AgNPs to some extent ameliorated these alterations and significantly improved its therapeutic efficacy against HepG2 cells. These findings indicate the potential use of GEM-AgNPs in the clinical setting for anticancer treatment.
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SE and MK conceived and designed this research. EO and AG conducted the experiments. MM did the histopathological investigations. EO and AG analyzed the data and wrote the manuscript. All authors read and approved the manuscript, and all data were generated in-house and that no paper mill was used.
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Animal handling and care, and the study design were revised and approved by Zagazig University, Egypt (ZU-IACUC/2/F/24/2020). The rats were euthanized after duly considering all ethical and humanitarian standards.
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El-Sheikh, S.M.A., Khairy, M.H., Osama, E. et al. Nanotechnology improves the therapeutic efficacy of gemcitabine against a human hepatocellular carcinoma cell line and minimizes its in vivo side effects. Naunyn-Schmiedeberg's Arch Pharmacol 394, 631–643 (2021). https://doi.org/10.1007/s00210-020-02004-y
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DOI: https://doi.org/10.1007/s00210-020-02004-y