(Tuesday, 7/31/2018) 4:30 PM - 6:00 PM
Room: Davidson Ballroom A
Purpose: To overcome the challenge of delivering the prescribed dose to cancer cells while sparing normal tissue, preferential introduction of high Z material to tumour cells works as a method of radiation sensitization. Gold nanoparticles (GNPs) are very useful in this respect. It has been shown that the size, shape, and surface properties of GNPs affect their cellular uptake. Manipulation of the cell cycle to arrest cells at different stages offers a unique strategy to study the molecular and structural events as the cell cycle progresses. To optimize delivery of GNPs into tumour cells and enhance the effect of radiosensitization. We investigated nanoparticle uptake in synchronized populations of MDMBA231 breast cancer cells
Methods: Populations of MDAMB231 cells were arrested in S-phase. Synchronized cells were incubated with 5nm GNP, 15nm GNP, and two formulations of liposome encapsulated 5nm GNPs. Uptake of nanoparticles is visualized using hyperspectral imaging and quantified with ICP-MS (Inductively Coupled Plasma Mass Spectrometry). Following internalization of gold nanoparticles, cells were irradiated with 6MV beams from linear accelerator, and the survival fraction and DNA damage were studied.
Results: Cell cycle analysis after a double-thymidine block shows the population is well synchronized. Uptake of nanoparticles is higher in synchronized cell population and is increased using liposome encapsulation delivery system. Ionizing radiation interacts with the GNPs inside of cells and produces secondary electrons that cause cellular damage. After a dose of 2Gy cell survival fraction is decreased following incubation with GNP indicating dose-enhancement.
Conclusion: After cell irradiation, clonogenic assays shows that when the uptake of GNPs is higher, there is a decrease in survival fraction and γ-H2AX immunofluorescent staining shows more DNA double strand breaks. Optimizing uptake of gold nanoparticles is important to fully take advantage of their radiosensitizer properties and the cell cycle is a factor to consider.
Funding Support, Disclosures, and Conflict of Interest: Funding for project from NSERC Discovery Grant
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