(Sunday, 7/12/2020) [Eastern Time (GMT-4)]
Room: AAPM ePoster Library
Purpose: Radiation dose enhancers such as gold nanoparticles (GNPs) in cancer cells has been tested to enhance the deposited radiation dose. However, the tumor microenvironment is a combination of stromal cells, such as normal fibroblasts (NFs) and cancer associated fibroblasts (CAFs) and simply targeting the tumor cells with GNPs will not be enough to eliminate a malignancy. The goal of this study was to understand the extent of GNP uptake and retention in normal vs cancers cells, and to elucidate the outcome when treated in combination with radiation.
Methods: For evaluation of the GNP uptake, HeLa, NFs, and CAFs were incubated with GNPs of 15nm diameter over a period of 24hrs. For studying the retention, cells were incubated with GNPs and left in fresh media over a period of 24hrs. A photon-based radiation dose of 2Gy was given using a clinical linear accelerator to ascertain radiation effects in the presence of GNPs. Assessment was completed using an immunofluorescent-based 53BP1 foci assay and a resazurin-based proliferation assay over a 14-day time period.
Results: CAFs had the largest uptake of the three cell lines, 265% of the uptake in HeLa, while NFs had the lowest at 2.87% of the uptake of CAFs. As a result, CAFs had a 13.5% increase in foci formation following radiation with GNPs compared to control, while HeLa and NFs had an increase of 9.8% and 8.8% respectively. CAFs did not see a decrease in survival fraction, however, relative to control, while a decrease was observed in HeLa and NFs.
Conclusion: Irradiated CAFs with GNPs did not see an appreciable difference in proliferation, despite increased uptake and increased DNA damage, relative to a radiated control while the other cell lines did, showcasing the complexity added to GNP-mediated dose enhancement in the tumor microenvironment by the addition of CAFs.
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