The cytotoxic enhancement of cisplatin by magnetic fluid hyperthermia (MFH) was investigated in human colon adenocarcinoma cells (Caco-2). A nanoparticle platform based on iron oxide functionalized with carboxymethyl dextran was employed to produce heat at the nanoscale. To assess the synergistic effect of hyperthermia and the anticancer drug cis-Diamminedichloroplatinum, commonly known as cisplatin (CIS), cell viability was measured 24, 48, and 72 hours after three different combined hyperthermia and CIS exposure sequences. These included CIS incubation prior to hyperthermia or magnetic fluid hyperthermia, CIS exposure only during hyperthermia or MFH, and additional CIS incubation following hyperthermia or MFH. Additional incubation of CIS after hyperthermia treatment appears to be more effective than prior CIS incubation for both hyperthermia treatments. Viability data also indicated that MFH combined with CIS is significantly more effective than hot water hyperthermia at the same temperature. A CIS concentration an order of magnitude lower than the calculated IC50 was found to be very effective in reducing cell viability. Such dramatic differences suggest that MFH may enhance the passive transport of CIS.
Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exposed to an oscillating magnetic field. Such energy dissipation can be employed to locally raise temperature inside a tumor between 41°C and 45°C (hyperthermia) to promote cell death, a treatment known as magnetic fluid hyperthermia (MFH). This work seeks to quantify differences between MFH and hot-water hyperthermia (HWH) in terms of reduction in cell viability using two cancer cell culture models, Caco-2 (human epithelial colorectal adenocarcinoma) and MCF-7 (human breast cancer). Magnetite nanoparticles were synthesized via the co-precipitation method and functionalized with adsorbed carboxymethyl dextran. Cytotoxicity studies indicated that in the absence of an oscillating magnetic field, cell viability was not affected at concentrations of up to 0.6 mg iron oxide/mL. MFH resulted in a significant decrease in cell viability when exposed to a magnetic field for 120 minutes and allowed to rest for 48 hours, compared with similar field applications, but with shorter resting time. The results presented here suggest that MFH most likely induces apoptosis in both cell types. When compared with HWH, MFH produced a significant reduction in cell viability, and these effects appear to be cell-type related.
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