Studies of ferrite based magnetic nanoparticle uptake and magnetocytolysis effects on model cell cultures

Suspended ferrite magnetic nanoparticles are known to dissipate energy under an oscillating magnetic field. Such energy dissipation could be employed to locally raise temperature inside a tumor to 41-45°C (hyperthermia), promoting cell death. This novel treatment is known as magnetic fluid hyperthermia (MFH). Even though clinical work has been conducted in relation to this phenomenon, little is known regarding the mechanisms of cell death and the main factors involved. This work focused on the examination of cell death mechanisms when an AC magnetic field is applied for a period of 120 min. The temperature range was maintained between 41°C and 45°C at a frequency of 237 kHz and a magnetic field of 2.8 kA/m. Two cell models (Caco-2 and MCF-7) were employed with distinct known properties. Magnetite nanoparticles were synthesized by coprecipitation and by thermodecomposition. Particles were functionalized with different polymers, such as commercial carboxymethyldextran, with 23-COOH or with 5-COOH, and poly(ethylene glycol). Cytotoxicity studies indicated that cell viability was not affected in the concentration range of 0.05-1.5 mg magnetite/mL. Results of nanoparticle uptake indicated that 0.15-0.20 pg magnetite/cell with MagCop-CMDXcom was internalized by both cell models, while MagTerm-PEG nanoparticles demonstrated a higher uptake by MCF-7 cells of 0.30 pg/cell for a period of 1 week, suggesting that nanoparticle uptake was affected by nanoparticles functionalization and cell type. MagCop-CMDXcom nanoparticles were selected to perform MFH experiments. Results indicated a significant decrease in cell viability for a magnetic field exposure of 120 min and a resting time of 24 hours when compared to similar field applications but with shorter resting times. MCF-7 cells appeared to be more sensitive to MFH than Caco-2 cells. The process of cell death appears to be mainly apoptotic. The results presented here suggest that apoptosis was likely induced during MFH and it has a higher effect on cell viability when compared to hyperthermia with hot water. This research proposed that MFH might be causing additional effects on cell death when compared to hyperthermia alone.