Biological mechanisms of gold nanoparticle-enhanced radiation therapy of prostate cancer
Mentor: Sri Sridhar, PhD (Northeastern University)
Radiation therapy is one of the most commonly used cancer treatments. It is damaging to not only cancer cells but also to healthy cells, limiting the amount of radiation that can be administered to patients. The combination of gold nanoparticles (GNPs) and radiotherapy has become a prominent area of research for cancer treatment. Previous research has shown that GNPs act as radiosensitizers, making cancerous cells more susceptible to radiotherapy. Using GNPs to kill more cancer cells with lower radiation doses reduces the severity of side effects. This characteristic can be attributed to gold's high atomic number and its ability to produce photoelectrons and Auger electrons. Photoelectrons are released when an inner shell electron absorbs a high-energy beam and leaves the atom in a high-energy state. Auger electrons are released when higher shell electrons move to an inner shell to stabilize the atom. These electrons are responsible for damaging cancer cells even further. Due to their low energy, they do not travel far from the cancer site and are less likely to damage healthy cells. Another advantage of using gold, compared to other high atomic number elements, is its imaging contrast, biocompatibility and lower toxicity (1). The aim of this research is to see how GNPs coupled with different radiation doses impact cellular mechanisms of the Capan-1 cell line. Radiation kills cancer cells by damaging their DNA or by creating free radicals that in turn damage DNA (1). By focusing on expression of proteins that are in relation with apoptosis, cell proliferation and DNA repair/damage as well as the change in reactive oxygen species within the cells, it is possible to see the cellular mechanisms of how GNPs radiosensitize cells. (1) Ngwa, W., Kumar, R., Sidhar S., Korideck, H., Zygmanski, P., Cormack, R., Berbeco, R., Makrigiorgos G. M. Targeted radiotherapy with gold nanoparticles: current status and future perspectives. Nanomedicine. (2014); 9(7): 1063-1082.
Confocal images of cells that have been treated with 2Gy radiation with (right) and without (left) GNPs. Blue represents a dapi staining of the nuclei, red represents the γH2AX protein, and green represents the Rad51 protein. γH2AX protein accumulates at DNA damage sites and is responsible for recruiting DNA repair proteins. It is commonly used as a DNA damage marker. Rad51 is another protein responsible for repairing DNA double strand breaks. As it can be seen with the image, cells pre-treated with GNPs have higher concentrations of γH2AX and Rad51 and hence did experience more DNA damage. Source: