Thesis Abstract
Background: Graphene oxide (GO) is a multifunctional carbon nanomaterial with tremendous potential in medical science including cancer therapy. It has unique physical, and chemical properties to be used as a drug carrier such as Doxorubicin (DOX). Aim: This study aimed to load DOX on (GO) and supramagnetic iron oxide GO (GO/Fe3O4) as a passive and active forms with or without folic acid (FA) and to compare the anti-tumor effects of these conjugates to free DOX.
Materials and Methods: GO was synthesized by Hummers method, then loaded with DOX, FA or Fe3O4. All conjugates were characterized by FT-IR, TEM and TGA techniques, then their anticancer properties were investigated in vitro using EAC cell lines. In vivo study was performed using EAC-bearing mice which were divided and treated with DOX, GO/DOX, rGO/DOX/FA, GO/Fe3O4/DOX, rGO/Fe3O4/FA/DOX, GO/Fe3O4/DOX+IR and rGO/Fe3O4/FA/DOX+IR. After 10 days, number of tumor cells, splenocytes and white blood cells (WBC), apoptosis, and cell cycle of tumor cells were analyzed. Results: In vivo results showed that GO conjugates induced significant decrease of the total numbers of EAC cells. Interestingly rGO/Fe3O4/FA/DOX+ IR treatment showed increases in late apoptosis whereas GO/DOX and rGO/Fe3O4/FA/DOX induced necrotic cells as compared to free DOX. Free DOX induced leukopenia in spleen, however treatment with GO/DOX or GO/FA/DOX induced lesser effects. Treatment with GO/DOX conjugates induced significant increases in the blood leukocytes as compared to treatment with DOX and GO/DOX/FA which induced leukopenia. Conclusion: These results demonstrate that GO composites may be a highly biocompatible nanomaterial with practical applications in cancer therapy.