(648a) Examination of the Enhanced Potentiation of Combined Cisplatin Treatment with Magnetic Fluid Hyperthermia | AIChE

(648a) Examination of the Enhanced Potentiation of Combined Cisplatin Treatment with Magnetic Fluid Hyperthermia

Authors 

Torres-Lugo, M. - Presenter, University of Puerto Rico, Mayaguez Campus
Rinaldi, C. - Presenter, University of Puerto Rico at Mayagüez
Soto, O. - Presenter, University of Puerto Rico, Mayaguez Campus
Castillo, A. - Presenter, University of Puerto Rico
Mendez, J. - Presenter, University of Puerto Rico
Rodriguez-Luccioni, H. L. - Presenter, University of Puerto Rico, Mayaguez Campus


Synergistic potentiation of platinum containing antineoplastic agents has been shown to be significantly improved by hyperthermia, but these classic modalities have demonstrated significant clinical challenges. Hyperthermia induced by magnetic nanoparticles, has the advantage of delivering thermal energy at the nano-scale, preventing side effects commonly observed in whole body and regional forms of hyperthermia. Previous work by us has demonstrated that combined Magnetic Fluid Hyperthermia (MFH) and Cisplatin (CIS) treatment caused a significant synergistic potentiation when compared to a similar treatment using hot water hyperthermia. Such differences could be the result of an increase in membrane permeabilization due to mechanical disruption of the cell membrane by MFH. To further investigate such phenomena, this work pursued the preliminary assessment of the potentiation effects of MFH in the absence of CIS active transport mechanism, also known as hCRT1. For this purpose, the Caco-2 cell line was employed. The active CIS transporter hCRT1 was saturated using Copper (Cu) (2µM) prior and during treatment. Cytotoxic effects of Cu were tested (IC50 ~150µM). Results indicated that the concentration employed did not cause any cytotoxic effects. To confirm the saturation of the active transport mechanism using the aforementioned concentration, the CIS IC50 with and without Cu was calculated. Results indicated that the CIS IC50 in the absence of Cu was 68µM whereas in the presence of the ligand the value significantly increased the IC50 to 126 µM. Combined MFH experiments with CIS (5µM) were conducted with and without the presence of Cu for 30 min at 41oC Cells were suspended (500,000 cells in 2.5 mL) in culture media with CIS, Cu, and dextran coated ferrite-based magnetic nanoparticles (0.6mg Fe/mL). Further CIS exposure was allowed after MFH for an additional 2h. This additional exposure was performed as recent work by us demonstrated that this sequence provided the highest reduction in cell viability when either MFH or hot water HT was performed. At this point, CIS was removed; cells were seeded on 75cm2 culture flasks, and allowed to recuperate for 48hrs. Results indicated that the aforementioned CIS concentration and the application of MFH for 30min at 41oC did not cause any significant reduction in cell viability. Interestingly, a significant reduction in cell viability was observed when MFH was applied in the presence of Cu. Such reduction may indicate that even though the main CIS transport occurs via the active hCRT1 mechanism, as evidenced by the combined treatment without Cu, still some increased CIS passive transport must have occurred to explain the reduction in cell viability. Such preliminary evidence suggests that passive transport could be enhanced by MFH.