(566a) Effects of Nanoparticle Properties On Cellullar Uptake and Magnetic Fluid Hyperthermia

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¢XC (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 mechanism 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. The temperature range was maintained between 41?aC and 45?aC 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 or by thermodecompositon. Particles were functionalized with different polymers, including commercial carboxymethyldextran, with 23-COOH or with 5COOH, and poly (ethylene glycol). Cytotoxicity studies performed during one week of exposure indicated that coprecipitated particles with commercial carboxymethyldextran demonstrated cytotoxic effects at concentrations higher than 0.9 mg magnetite/mL, while cell viability was not affected in the concentration range of 0.05-1.5 mg magnetite/mL with nanoparticles synthesized by thermodecomposition. Nanoparticle uptake was performed utilizing carboxymethyl dextran with various degrees of substitution. The purpose of these experiments was to elucidate the effects of charge on particle internalization utilizing the same polymer chain. Results indicated that particle uptake was in the range of 0.5-0.6 pg magnetite/cell with magnetite-CMDX (~23 COOH groups/chain). Magnetite-CMDX5COOH demonstrated no internalization in both cell models, suggesting that the degree of substitution showed an effect on particle uptake. On the other hand Magnetite-PEG nanoparticles demonstrated the highest uptake by MCF-7 cells of 0.8-1.0 pg/cell. These results suggest that nanoparticle uptake was affected by nanoparticles functionalization and cell type. Magnetite-CMDX nanoparticles were selected to perform MFH experiments. Hot water hyperthermia was performed and compared with magnetic fluid hyperthermia. Magnetic fluid hyperthermia exposure times (i.e application of magnetic field) were 60 min and 120 min. Cell viability was measured immediately after treatment, 24 or 48 hours after treatment. Results related to hot water hyperthermia indicated that cell viability effects were observed 48 hours after treatment, while the effects on cell viability of magnetic fluid hyperthermia were detected 24 hours after treatment. Results indicated a significant reduction in cell viability for a magnetic field exposure of 120 min and a resting time of 48 hours when compared to hot water hyperthermia. Hot water hyperthermia decreased cell viability to 30-45% while magnetic fluid hyperthermia decreased cell viability almost completely, 2-5%. 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 hot water hyperthermia. These results also suggest that MFH might be causing additional effects on cell viability when compared to hot water hyperthermia.