Abstract
By taking the advantage of supraparamagnetic graphene oxide (GO/Fe3O4) hybrid nanocomposite, as a drug delivery system with high thermal conductivity without altering its anti-tumor efficacy, this study aimed to investigate the behavior of doxorubicin (DOX) loaded onto GO/Fe(3)O(4)as passive (GO/Fe3O4/DOX) or with folic acid (FA) as active (GO/Fe3O4/FA/DOX) hybrid form before and after external exposure to infrared radiation (IR), as a hyperthermia source. In addition to investigation of its anti-tumor actions and the associated cardiotoxicity effect, the conjugates were characterized by using TEM, FT-IR, and TGA analysis. Ehrlich ascites carcinoma (EAC) breast cancer cell line was used to assess the anti-tumor effects of these conjugates in vivo. The results confirmed the nanosize of conjugates, which showed high loading capacity surface area for DOX reaching up to 90%. Although the conjugates showed strong anti-tumor effects similar to those of DOX, they expressed different impacts on cell cycle and apoptosis of EAC cells. Additionally, when the conjugates were stimulated with IR, the level of creatine kinase-MB (CK-MB) as a cardiac biomarker was close to normal level. In conclusion, active (GO/Fe3O4/FA/DOX) hybrid form in combination with brief hyperthermia induces anti-tumor effect with less cardiotoxicity. Further studies are needed to optimize the beneficial effects of this kind of hyperthermia and to understand the underlying mechanisms.