N-Hydroxysuccinamide functionalized iron oxide nanoparticles conjugated with 5-flurouracil for hyperthermic therapy of malignant liver cancer cells by DNA repair disruption

Abstract

Magnetized iron oxide nanoparticles are ideal materials for biological and biomedical applications due to their biocompatibility, super paramagnetic behavior, surface capability, and chemical stability. This research article is narrating the overview of methodologies of preparation, functionalization, characterization and applications of Fe₃O₄ nanoparticles. Super paramagnetic nanoparticles are studied for their hyperthermia properties. The proposed mechanism behind the hyperthermia was damaging the proteins responsible for DNA repair thereby, directly accelerating the DNA damages on cancer cells by increasing the temperature in the vicinity of the cancer cells. In this study, super paramagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) and anti-cancer drug, 5-fluorouracil, functionalized with N-Hydroxysuccinimide organic molecules. A specific absorption rate at 351 nm can be achieved using UV analysis. The magnetic Fe₃O₄ nanoparticles had a cubic crystalline structure. FE-SEM(field emission scanning Electron microscopy) with EDAX(energy dispersive X-ray analysis) analysis shows that the size of the SPION was about 30-100 nm range and the percentage of chemical compositions was higher in the order of Fe, O, C. for particle size analysis, the SPION were positively charged derived at +9.9 mV and its conductivity is measured at 0.826 mS/cm. In-vitro anti-cancerous activity analysis in Hep-G2 cells (liver cancer cells) shows that the 5-fluorouracil functionalized SPIONs have higher inhibition rate than the bare Fe₃O₄ nanoparticles. The Fe₃O₄ nanoparticles were studied for their hyperthermic abilities at two different frequencies such as 3.05 × 10⁶ kAm^-1s^-1 and 4.58 × 10⁶ kAm^-1s^-1.The bare Fe₃O₄ at low magnetic field, 10 mg was required to raise the temperature above 42°- 45 °C and at high magnetic field, 6 mg was enough to raise the same temperature. The 5-fluorouracil functionalized Fe₃O₄ shows that at low magnetic field, 6 mg is required to raise the hyperthermia temperature and at high magnetic field, 3 mg is required to raise the temperature above 42°- 45 °C. the rate of heating and the temperature achieved with time can be tuned with concentrations as well as magnetic component present in the Fe₃O₄ nanoparticles. Beyond this concentration, the rate of cell death was observed to increase. The saturation and low residual magnetization were revealed by the magnetization analysis, making them well suited for clinical applications.

Keywords: 5-Fluorouracil; Alternating magnetic field; Anti-cancer drug; Fe(3)O(4) nanoparticles; Magnetic hyperthermia; SPIONs (super para magnetic iron nanoparticles); Tumor cells Etc.