الفهرس 
Cancer
NanomedicineOnly 14 pages are availabe for public view
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Abstract
The main objective of this study was to enhance efficacy of cancer chemotherapy as doxorubicin with lower toxicity through nanotechnology by selecting nanomaterial as GO with suitable properties and could be chemically manipulated cause of unique structure and geometry as a single layer of carbon atoms arranged in a honeycomb with two dimensional crystal with sp2 hybridization, so has important properties whether chemically or physically as excellent thermal and electrical conductor, large suitable surface area and bio-compatibility, then loaded with chemotherapy drug and targeted internally through conjugation by FA as active targeting form to folate receptor on cancer cells. GO, a new type of nanomaterial in the carbon family, was prepared by Hummers method and used as adsorbent for DOX from aqueous solution. The physico-chemical properties of GO were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), zeta potential, and element analysis. The adsorption properties of DOX on GO were studied as a function of contact time, adsorbent dosage, temperature and pH value. GO was loaded by DOX with or without FA to compare between passive or active which could be more effective, also GO/Fe3O4 was stimulated externally by IR radiation to evaluate the combination of drug delivery system and hyperthermia effect as anticancer. characterization of GO NPs conjugates showed that they are in nano size form. The loading capacity of DOX on GO was 91% and 94% on GO Fe3O4, but decreased to 54% with FA that was 88% as initial concentration, these ratios was taken under consideration to be adjusted later. In vitro study revealed that GO NPs conjugates significantly reduced viability of EAC cells. In vivo study with DOX loaded (15 mg/kg) compared to free DOX (15 mg/kg) as a single dose at day1 then EAC-bearing mice were sacrificed at day10 to evaluate ant-cancer and cytoxicity effect of the treatment with GO/DOX, rGO/FA/DOX, GO/Fe3O4/DOX, rGO/Fe3O4/FA/DOX, GO/Fe3O4/DOX.+IR and rGO/Fe3O4/FA/DOX+IR. DNA content during the cell cycles of EAC cells was determined by flow cytometry using PI (Propidium iodide) fluorescent stain. All treatments showed significant anticancer effect on EAC, especially active form, but each treatment had its own mechanism which be recorded by EAC cell cycle and apoptosis analysis, as with regard to cell cycle we found that GO/DOX, GO/Fe3O4/DOX and GO/DOX/FA, rGO/Fe3O4/FA/DOX treatments arrested the cell cycle at G0/G1 or S phase, respectively, as both induced significant decrease in the number of tumor cells at G2/M phase, while free DOX and GO/Fe3O4/DOX+IR induced tumor cell cycle arrest at subG0 phase. Apoptosis analysis of EAC cells using (AnnexinV–PI) showed that rGO/FA/DOX and rGO/Fe3O4/FA/DOX+ IR treatment highly increased apoptosis in late apoptosis as well as GO/DOX and rGO/Fe3O4/FA/DOX treatments greatly induced necrosis of EAC cells as compared to free DOX, concluding that GO NPs conjugates induced anti-tumor in EAC-bearing mice. Also sGPT activity decreased with GO/DOX, GO/Fe3O4/DOX and GO/DOX/FA, while CK.MB was decreased after treatment with two forms of radiated DOX loade GO/Fe3O4. GO NPs conjugates resulted in low cytotoxicity compared to dox treatment, as we noticed marked increase in number of splenocytes however, WBCs need more time to recover compared to free DOX-treatment. Taken together, our findings substantiated that GO NPs conjugates induced cytotoxicity, apoptosis, and cell cycle arrest in EAC cells, hence conjugates may be potentially applied to breast cancer treatment as a powerful synergis t ic agent with DOX or any other chemotherapeutic agents. Conclusion Development of anticancer agents that can induce apoptosis is an attractive target for cancer cure and treatment. In this study, we have investigated the anticancer property of synthesized composites of graphene oxide (GO/DOX and GO/DOX/FA) in-invitro and in-vivo. These compounds decreased viability of EAC cells in-vitro and they showed anticancer activity and arrested the cell cycle at G0/G1 phase or S-phase inducing cell death by apoptosis. Interestingly, GO/DOX/FA has a potent anticancer activit y enhancing EAC apoptosis and reduces bad side effects of chemotherapeut ic agent DOX on normal cells. These results demonstrate that GO composites may be a highly biocompatible nanomaterial with practical applications in cancer therapy. Although the clinical significance of our findings remains to be elucidated, the information may contribute to a better understanding of the interactions between EAC cells and GO nanomaterials.