Internalized Nanoceria Modify the Radiation-Sensitivity Profile of MDA MB231 Breast Carcinoma Cells

SIMPLE SUMMARY: Cerium oxide nanoparticles (nanoceria) influence its environment by donating or accepting electrons readily. We investigated nanoceria’s ability to modify the health of treatment-resistant breast cancer cell type, with various doses of potentially damaging radiation. We used electron microscopy to determine the presence and location of various amounts of nanoceria in cells. We also used imaging modalities such as confocal fluorescence and flow cytometry to study cell-health, cell-death, and amounts of potentially damaging unstable molecules called reactive oxygen species, all without or with different doses of radiation. Our results showed that nanoceria were taken up by a cell-drinking process called macropinocytosis, and then got segregated into large compartments called macropinosomes. There was an overall decrease in cell-death with increasing nanoparticle concentrations. This increase in cell-health resulted in a reduction of the reactive oxygen species at all tested radiation doses. Moreover, this effect appeared prominent at lower radiation doses compared to populations not treated with radiation or nanoparticles. In conclusion, our discovery shows that internalized nanoceria provide protection from radiation with a corresponding decrease in reactive oxygen species in this type of breast cancer cells and this property confers significant perils and opportunities when utilized in the context of cancer radiation therapy. ABSTRACT: Owing to its unique redox properties, cerium oxide (nanoceria) nanoparticles have been shown to confer either radiosensitization or radioprotection to human cells. We investigated nanoceria’s ability to modify cellular health and reactive oxygen species (ROS) at various absorbed doses (Gray) of ionizing radiation in MDA-MB231 breast carcinoma cells. We used transmission electron microscopy to visualize the uptake and compartmental localization of nanoceria within cells at various treatment concentrations. The effects on apoptosis and other cellular health parameters were assessed using confocal fluorescence imaging and flow cytometry without and with various absorbed doses of ionizing radiation, along with intracellular ROS levels. Our results showed that nanoceria were taken up into cells mainly by macropinocytosis and segregated into concentration-dependent large aggregates in macropinosomes. Confocal imaging and flow cytometry data showed an overall decrease in apoptotic cell populations in proportion to increasing nanoparticle concentrations. This increase in cellular health was observed with a corresponding reduction in ROS at all tested absorbed doses. Moreover, this effect appeared pronounced at lower doses compared to unirradiated or untreated populations. In conclusion, internalized nanoceria confers radioprotection with a corresponding decrease in ROS in MDA-MB231 cells, and this property confers significant perils and opportunities when utilized in the context of radiotherapy.