నానోమెడిసిన్ & నానోటెక్నాలజీ జర్నల్

నైరూప్య

Cellular Uptake and Radio-sensitization Effect of Small Gold Nanoparticles in MCF-7 Breast Cancer Cells

Branislava Janic, Fangchao Liu, Kevin R Bobbitt, Stephen L Brown, Indrin J Chetty, Guangzhao Mao, Benjamin Movsas and Ning Wen

Gold nanoparticles (AuNPs) are shown to increase cancer cells sensitization to ionizing radiation. Theoretical models predicted that due to the differences in absorption coefficient between gold and soft tissue, maximum sensitization can be achieved at kilovoltage (kV), with minimum to no effect at megavoltage (MV) range, which was indeed demonstrated by previous research on AuNPs radio-sensitization with kV radiation. However, AuNPs effect at MV energies is still not clear. Radio-sensitization depends on AuNPs’ internalization by cancer cells that is in turn affected by AuNPs size. The purpose of this study was to explore, in vitro, radio sensitization potential of AuNPs of 4 and 14 nm size with clinically relevant MV, as well as kV photons in MCF7 breast cancer cell line. We investigated the differences in cellular uptake and intracellular localization between 4 and 14 nm AuNPs by transmission electron microscopy (TEM). We also examined the effect of these AuNPs on MCF7 cells response to irradiation by MTT analysis of cell proliferation, and flow cytometry analysis of H2AX phosphorylation as an indicator of DNA double strand breaks (DSBs). Our results demonstrated significant AuNPs cellular uptake and a selective, size dependent intracellular localization with 4 nm AuNPs mostly residing in cytoplasm and 14 nm in nucleus. Nanoparticles of both sizes sensitized MCF-7 breast cancer cells to radiation at both kV and MV energies, independent of particle size. Radio-sensitization was detected as an increase in radiation induced inhibition of cell proliferation and radiation induced DNA DSBs. This work provides valuable information for further exploring mechanisms of AuNPs radio-sensitization in cancer cell lines that may be important in designing and optimizing AuNPs based radiotherapies.