Abstract
Cerium oxide nanoparticles have been shown to sensitize cancer cells to radiation damage. Their unique redox properties confer excellent therapeutic potential by augmenting radiation dose with reactive oxygen species mediating bystander effects. Owing to its metallic properties, cerium oxide nanoparticles can be visualized inside cells using reflected light and optical sectioning. This can be advantageous in settings requiring none or minimal sample preparation and modification. We investigated the use of reflectance imaging for the detection of unmodified nanoceria in MDA MB231 breast cancer cells along with differential interference contrast imaging and fluorescent nuclear labeling. We also performed studies to evaluate the uptake capability, cellular toxicity and redox properties of nanocaria in these cells. Our results demonstrate that reflectance structured illumination imaging can effectively localize cerium oxide nanoparticles in breast cancer cells, and when combining with differential interference contrast and fluorescent cell label imaging, effective compartmental localization of the nanoparticles can be achieved. The total number of cells taking up the nanoparticles and the amount of nanoparticle uptake increased significantly in proportion to the dose, with no adverse effects on cell survival. Moreover, significant reduction in reactive oxygen species was also observed in proportion to increasing nanoceria concentrations attesting to its ability to modulate oxidative stress. In conclusion, this work serves as a pre-clinical scientific evaluation of the effective use of reflectance structured illumination imaging of cerium oxide nanoparticles in breast cancer cells and the safe use of these nanoparticles in MDA MB231 cells for further therapeutic applications.
Highlights
Nuclear medicine and radiation therapy are among the most effective cancer treatments available and more than half of the cancer patients undergo ionizing radiation therapy owing to its ability to eradicate primary and metastatic solid tumors, cancer stem cells, as well as microscopic tumor extensions [1]
The effectiveness of radiation to eliminate cancer cells is by directly interacting with critical cell targets [2] or indirectly by free radical production, the latter leading to increased apoptosis of cells [3]
One main challenge of traditional radiation therapy is that tumors can be located close to normal tissue or near organs at risk that can limit the amount of radiation dose delivered to the target volume [4]
Summary
Nuclear medicine and radiation therapy are among the most effective cancer treatments available and more than half of the cancer patients undergo ionizing radiation therapy owing to its ability to eradicate primary and metastatic solid tumors, cancer stem cells, as well as microscopic tumor extensions [1]. Our studies used a unique and relatively novel approach to localize unmodified and unlabeled cerium oxide nanoparticles in the triple negative breast cancer cell line, MDA MB231. We hypothesized that naked cerium oxide nanoparticles can be effectively localized in breast cancer tumor cells and the localized nanoceria will be safe for further biomedical applications. This hypothesis was tested in MDA MB231 cells using reflectance structured illumination imaging, flow cytometry, cell survival and reactive oxygen species assays
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