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PURPOSE: In this study the effect of PLGA polymeric nanoparticles as a 5-fluorouracil (5-FU) carrier with and without iron oxide core and hyperthermia were investigated on the level of DNA damage in a spheroid culture model of HT-29 colon cancer cell lines by alkaline comet assay. MATERIALS AND METHODS: First, HT-29 colon cancer cells were cultured in vitro as spheroids with a mean diameter of 100 µm. The spheroids were then treated with different concentrations of 5-FU or nanoparticles as 5-FU carriers with and without an iron oxide core for one volume-doubling time of the spheroids (71 h) and hyperthermia at 43 °C for 1 h. Finally, the effect of treatment on viability and level of DNA damage was examined using trypan blue dye exclusion assay and alkaline comet assay, respectively. RESULTS: Results showed that hyperthermia in combination with 5-FU or nanoparticles as 5-FU carriers significantly induced the most DNA damage as compared with the control group. The extent of DNA damage following treatment with 5-FU-loaded nanoparticles combined with hyperthermia was significantly more than for 5-FU combined with hyperthermia. In comparison to the effect of 5-FU-loaded nanoparticles with the iron oxide core and 5-FU-loaded nanoparticle without the iron oxide core, the nanoparticles with the iron oxide core combined with hyperthermia induced more DNA damage than the nanoparticles without the iron oxide core. CONCLUSIONS: According to this study, hyperthermia is a harmful agent and nanoparticles are effective delivery vehicles for drugs into colon cancer cells. The iron oxide filled nanoparticles increased the effect of the hyperthermia. All these factors have a significant role in the treatment of colorectal cancer cells.
Esmaelbeygi et al. (Mon,) studied this question.