الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Oral squamous cell carcinoma (OSCC) among the most frequent cancerous tumors in humans. The most common site of OSCC is TSCC, which is highly aggressive and can lead to lymph node or distant organ metastases, lowering the patient’s overall survival rate. Chemotherapy has been the standard treatment for both localized and metastatic cancers until now. However, it is not particularly successful due to various constraints (low aqueous solubility, lack of anticancer drug selectivity, multidrug resistance, and so on). Nanotechnology represents innovative and more efficient nanotechnology based medication delivery vehicles solutions to promote oral and intravenous treatment approaches in order to address the drawbacks of present cancer therapy procedures. Chitosan has been utilized as a carrier in polymeric nanoparticles to deliver drugs via a variety of ways. In recent years, chitosan has demonstrated tremendous promise as a medication delivery vehicle. Various mixtures of a cytotoxic agent and an antioxidant have been shown to be beneficial on different types of cancer in the literature. It has been demonstrated that using 5-FU and the Qu together has synergistic effects in pancreatic cancer treatment. To our knowledge, however, this combination has not been studied for the treatment of oral cancer in English literature. Accordingly, the aim of this study was to assess the effect of quercetinloaded chitosan nanoparticles (Qu-ChNPs), 5-FU-loaded chitosan nanoparticles (5-FU-ChNPs) and dual drug-loaded chitosan nanoparticles (Qu and (5-FU)-ChNPs) on TSCC cell line. Tongue SCC cell lines (SCC-25) were used. ChNPs, Qu-ChNPs, (5- FU)-ChNPs, and dual Qu and (5-FU)-ChNPs were prepared and characterized using TEM and SEM. The TSCC cell line (SCC25) was subcultured to obtain 5 groups, which were subjected to 5-FU (as a positive control), Qu-ChNPs, 5FU-ChNPs, and dual Qu and 5-FU-ChNPs in addition to one group not subjected to any of these compounds (as a negative control (NC). First of all, Qu-ChNPs, 5FU-ChNPs, and dual Qu and (5-FU)-ChNPs were prepared and characterized. Second, the study groups were assessed using the MTT viability assay followed by the IC50 calculation. Then, the cell cycle and apoptosis analysis in the different groups were evaluated by flow cytometry using the IC50 dose, and immunocytochemistry for visualization of apoptosis by caspase3 marker was used. Finally, cell invasion and migration were assessed through wound healing assay. The present results showed that ChNPs, Qu-ChNPs, (5-FU)-ChNPs, and the dual Qu and (5-FU)-ChNPs were prepared and employed for drug release in treatment of TSCC. The present results revealed that Qu-ChNPs, (5-FU)-ChNPs, and the dual Qu and (5-FU)-ChNPs had antiproliferative effect against TSCC cells which was evaluated by MTT assay. Concerning the cell cycle arrest and apoptosis effect of Qu-ChNPs, (5-FU)-ChNPs, and the dual Qu and (5-FU)-ChNPs, the present result detected an induction of these compounds to cell cycle arrest and to apoptosis of TSCC cells which was evaluated by flow cytometry assay and the apoptotic cells were visualized by detection of caspase 3 through immunocytochemistry. In this study, the antimigratory effect of Qu-ChNPs, (5-FU)-ChNPs, and the dual Qu and (5-FU)-ChNPs was revealed by using wound healing assay. Results of the present work revealed that Qu and 5-FU had a good synergistic effect against TSCC cells. Statistical analysis of the present study showed a highly significant difference on comparing percentage of viable cells in different cell cycle phases, percentage of apoptosis, percentage of migratory cells, levels of caspase 3 among all the studied groups. In conclusion, chitosan NPs are good candidates for being employed as a carrier in TSCC therapy and that Qu-ChNPs, (5-FU)-ChNPs, and dual Qu and (5-FU)-ChNPs have promising effects against TSCC cell lines.