DOI: 10.3390/ijms27198632 ISSN: 1422-0067

Radiosensitizing Effect of Gold Nanoparticles Stabilized with Sodium Citrate and Thioglycolic Acid on MDA-MB-231 and MCF7 Breast Cancer Cells

Anna Smirnova, Elizaveta Kontareva, Zain Nofal, Valery Kryuchikhin, Anna Chigasova, Nikita Drozhzhin, Evgeny Andreev, Irina Fadeikina, Alisher Mutali, Alexander Nechaev, Sergey Leonov, Andreyan N. Osipov, Margarita Pustovalova

Gold nanoparticles (AuNP) have been increasingly investigated as potential radiosensitizing agents for the treatment of cancer. In the present study, AuNP stabilized with sodium citrate and thioglycolic acid (AuNP-Cit-TGA) were synthesized to assess their radiosensitizing effects on MDA-MB-231 and MCF7 breast cancer cells after X-ray exposure. The AuNP-Cit-TGA displayed an average diameter of 22 nm, showcasing extremely low hemolytic activity in vitro, along with a moderate rate of cellular uptake. AuNP-Cit-TGA notably decreased cell viability in both cell lines 48 h after exposure to a radiation dose of 6 Gy, as demonstrated by the Alamar Blue assay. Dose–response clonogenic assay indicated a significant decrease in the survival of nanoparticle-treated MCF7 cells compared to control groups. This decrease was associated with heightened oxidative stress, as evidenced by increased DCFH fluorescence and a decrease in the expression of SOD2, GPx1, CAT, and TXRDN1 genes 24 h following 2 Gy exposure. Remarkably, the uptake of AuNP-Cit-TGA enhanced the occurrence of single-strand DNA breaks in MCF7 cells by nearly double when compared to radiation treatment alone. However, this effect was not statistically significant in MDA-MB-231 cells. Despite this, residual γH2AX and 53BP1 foci were observed in both cell lines, revealing ongoing unrepaired DNA double-strand breaks connected to the uptake of nanoparticles by cells. Collectively, these findings provide valuable insights into the application of AuNP-Cit-TGA as an effective radiosensitizing agent in breast cancer radiotherapy.