Superparamagnetic graphene oxide/magnetite nanocomposite delivery system for doxorubicin-induced distinguished tumor cel

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RESEARCH PAPER

Superparamagnetic graphene oxide/magnetite nanocomposite delivery system for doxorubicin-induced distinguished tumor cell cycle arrest and apoptosis Mohamed L. Salem & Ali Gemeay & Soha Gomaa & Maha A. Aldubayan & Lobna Assy

Received: 30 January 2020 / Accepted: 25 June 2020 # Springer Nature B.V. 2020

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/Fe3O4 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. Keywords Anti-tumor . Apoptosis . Cardiotoxicity . Cell cycle . Doxorubicin . Ehrlich ascites carcinoma . Hyperthermia . Superparamagnetic.

This article is part of the Topical Collection: Nanotechnology in Arab Countries, Guest Editor, Sherif El-Eskandarany M. L. Salem : S. Gomaa : L. Assy (*) Immunology and Biotechnology Unit, Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt e-mail: [email protected] M. L. Salem : L. Assy Center of Excellence in Cancer Research, Tanta University, Teaching Hospital, Tanta University, Tanta, Egypt A. Gemeay Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt M. A. Aldubayan Pharmacology and Toxicology Department, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia

Introduction Graphene oxide (GO) is a single atom thick sheet of sp2 hybridized carbon atoms arranged in a hexagonal lattice, with remarkable physical and chemical characteristics including high mechanical properties, large surface area, and good thermal and electrical conductivity (Feng and Liu 2011; Muazim and Hussain 2017; Sanchez et al. 2012). Superparamagnetic graphene oxide (GO/Fe3O4) nanoparticles, as hybrid nanocomposite of GO and Fe3O4, are widely recognized for their safety and eff