Abstract
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.
Acknowledgements
This work was supported by grant No. 21533 from the School of Medicine, Iran University of Medical Sciences (IUMS).
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.