الفهرس 
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Abstract
SUMMARY AND CONCLUSION
Nanomedicine is nowadays an important tool in cancer. Advances in this direction will have an invaluable impact on disease management and improving the quality of life for patient. One of the most important well known nanoparticles used successfully for treatment of cancer is nanozinc.
Zinc plays a vital role in metabolic process as an essential trace element with antioxidant properties and furthermore, as a key constituent or cofactor of many proteins, zinc might be critical in host defence against the initiation and progression of cancer. The role of zinc in cancer has received increasing attention as a link between zinc deficiency and cancer has now been established in human studies.
Zinc oxide nanoparticles have received much attention for their implications in cancer therapy. It has been reported that Zinc oxide nanoparticles induce selective killing of cancer cells. Specific properties and characteristics of ZnO nanoparticles, such as their inherent toxicity against cancerous cells, at least for cells of lymphocytic origin, their ability to induce intracellular ROS generation leading to death via an apoptotic mechanism, and their physiochemical properties leading to cellular uptake and ease of functionalization make them an appealing candidate for biomedical applications.
Ionic liquids have also attracted the scientific community’s due to their pharmaceutical properties such as anticancer activities. The
SUMMARY AND CONCLUSION anticancer activity and cytotoxicity of phosphonium and ammonium-based ILs have been determined for the first time via American National Cancer Institute’s (NCI’s) in in vitro 60 human tumor cell lines. In general, phosphonium-based ILs were found to be more active and less cytotoxic as compared to ammonium ILs.
The present study was performed to estimate the effect of zinc nanoparticles alone or together with phosphonium ionic liquid for treatment of cancer in vitro and in vivo.
Two types of cell lines were used in this study. (1) The experimental cell line Ehrlich carcinoma (EC) and (2) human liver carcinoma cell line (HepG2). The in vitro study was conducted to evaluate the cytotoxic effect of zinc nanoparticles (Zn np), trihexyl (tetradecyl) phosphonium chloride ionic liquid (IL) and zinc nanoparticles suspension in trihexyl (tetradecyl) phosphonium chloride ionic liquid (Zn np suspension in an IL) on the chosen cell lines either by trypan blue exclusion method or crystal violet cytotoxicity assay. Results showed potent effect of Zn np suspension in an IL more than Zn np and IL in a dose dependent manner, where increasing concentration of the compound resulted in increased percentage of dead cells.
A total number of 160 adult female Swiss albino mice (22-25 g) divided into 8 equal groups were used for in vivo experiments:
Group (1) control group, Group (2) mice treated with Zn np (100 mg/kg/day), Group (3) mice treated with IL (37.6 mg/kg/day), Group (4) mice treated with Zn np suspension in an IL (75 mg/kg/day), Group (5) Ehrlich ascites carcinoma inoculated mice,
Group (6) Ehrlich ascites carcinoma inoculated mice and administered Zn np (100 mg/kg/day) Group (7) Ehrlich ascites carcinoma inoculated mice and administered IL (37.6 mg/kg/day) Group (8) Ehrlich ascites carcinoma inoculated mice and administered Zn np suspension in an IL (75 mg/kg/day).
All animal groups were sacrificed after 31 days, blood, liver and tumor samples were taken and the biochemical parameters including antioxidant activity (CAT, SOD, GSH and GPx) and lipid peroxidation level in blood and tissue as well as determination of liver function parameters (protein, albumin, ALT, AST), kidney function parameters (urea, creatinine), tumor necrosis factor-alpha (TNF-α) and interleukin-10, were investigated. Parts of liver and tumor tissues were used for histopathological investigations.
The results of the present study can be summarized as follows:
1- Inoculation with Ehrlich ascites carcinoma was able to induce oxidative stress, which was manifested by high level of MDA which was accompanied by depletion in GSH and inhibition in the antioxidant defending enzymes (GPx, CAT and SOD).
Besides, AST, ALT, urea and creatinine showed a remarkable increase. On the other hand a decrease in protein level and increase in TNF-α level was also observed.
2- On pretreatment with Zn np, IL and Zn np suspension in an IL, amelioration in MDA level was achieved; also GSH level and activities of antioxidant enzymes (GPx, CAT and SOD) were improved.
A remarkable amelioration in liver, kidney functions tests was also observed.
Administration of Zn np and Zn np suspension decreased liver TNF-α level than in EAC mice. Also different treatments increased the production of TNF-α and interleukin-10 in tumor tissue homogenate compared to EAC group.
3- Pretreatment with Zn np and phosphonium based ionic liquid resulted in necrosis of cancer cells and pretreatment with Zn np suspension in phoshonium ionic liquid showed necrosis in most of cancer cells.
In conclusion results revealed the synergetic antitumor effect between trihexyl (tetradecyl) phosphonium chloride ionic liquid and zinc nanoparticles.
Administration of zinc nanoparticles suspension in trihexyl (tetradecyl) phosphonium chloride ionic liquid has achieved its protective goal in reduction of cancer cells and defense against oxidative stress and tissue damage caused by Ehrlich ascites carcinoma which suggest that zinc nanoparticles suspension in trihexyl (tetradecyl) phosphonium chloride ionic liquid may potentially presents new hope for the development of new cancer therapeutics, which should attract further scientific and pharmaceutical interest.