Synthesis of Functionalized Magnetite (Fe3o4) Nanoparticles and Targeting to the Tumour Cell (Hela) For Cancer Diagnosis and Treatment

Abstract

Cancer is one of the global problems of this century and responsible for the death of one in 8 men and one in 11 women worldwide today. By 2040, 29.5 million new cancer cases are estimated to occur by the International Agency for Research on Cancer (IARC). It is a great need for the development of current cancer diagnosis and treatment methods. This dissertation aims to synthesize monodisperse spherical and/or cubic superparamagnetic Fe3O4 nanoparticles which have potential applications in cancer diagnosis and cancer treatment and investigate in vitro their cytotoxicity on human cervical carcinoma (HeLa) cells. In the presented study, 8.4±1.0 nm spherical and 8.3±1.1 nm, 14.4±0.6 nm, 24.5±1.9 nm cubic highly monodisperse, superparamagnetic iron oxide nanoparticles were synthesized by thermal decomposition method. To render them convenient for biomedical applications, they were coated with meso-2,3-Dimercaptosuccinic acid (DMSA) via ligand exchange reaction. The spherical nanoparticles were also functionalized with (3-Aminopropyl)triethoxysilane (APTES) and 2-deoxy-D-glucose (DG) to investigate the effects of surface functionality on their magnetic properties and their cytotoxicities. The structural and magnetic properties of the nanoparticles were characterized comprehensively and systematically by using X-ray diffraction (XRD), transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), zeta sizer, thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), inductively coupled plasma mass spectrometry (ICP-MS). Magneto-thermal properties of the water-soluble nanoparticles were measured by an instrument for magnetic hyperthermia. The cytotoxicity of the spherical nanoparticles with three different coatings and DMSA coated cubic nanoparticles with three different sizes were assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells incubated with the nanoparticles for 72 h were stained with Prussian blue and visualized by an inverted microscope to determine intracellular uptake of nanoparticles. The results indicated that the water-soluble nanoparticles with different surface properties such as size, shape and charge caused no significant toxic effects on HeLa cell viability under the tested nanoparticle concentrations and incubation times. Specific absorption rate (SAR) value of the 24.5 nm cubic Fe3O4 nanoparticles was determined as 197.4 W/gFe under 15.95 kA/m alternative current (AC) magnetic field and 488 kHz frequency, resulting in a temperature rise of 15 ̊C in about 5 minutes. The results show a very promising potential on the use of the surface-functionalized Fe3O4 nanoparticles for clinical trials in cancer diagnosis and treatment.