Radiosensitizing effects of silver nanoparticles targeting angiogenesis and matrix metalloproteinase signaling in triple negative breast cancer cell lines

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with few treatment options and limited response to radiation therapy due to radioresistance. This study explores the anti-angiogenic and anti-migratory potential of silver nanoparticles (Ag-NPs) as radiosensitizers in TNBC cell lines (MDA-MB-231 and MDA-MB-468). Cells were exposed to Ag-NPs and RT. Cell viability was assessed by MTT and trypan blue exclusion assay. Apoptosis and intracellular reactive oxygen species (ROS) were detected by flow cytometry. Angiogenesis-related genes were evaluated by qPCR, while MMP2 and MMP9 protein levels were determined by western blotting. Cell migration and tube formation were assessed using a scratch assay and an endothelial tube formation assay, respectively. Combination of Ag-NPs with RT exhibited strong synergistic anticancer effects in TNBC cell lines. The combinational treatment significantly enhanced apoptosis and ROS production compared to control and individual treatments. It also reduced VEGFR2 and Tie2 gene expression in both cell lines and decreased MMP2 and MMP9 protein levels in MDA-MB-231 cells. Cell migration and tube formation were significantly impaired in MDA-MB-231 cells exposed to combination therapy. Ag-NPs enhanced the cytotoxic effects of RT in TNBC cell lines by increasing apoptosis and ROS, and suppressing cell migration and angiogenic activity, suggesting their potential as a radiosensitizer to improve therapeutic strategies.