X-ray-Sensitive Selenium Nanoparticles Enhance Esophageal Squamous Cell Carcinoma Radiotherapy through Activating P53/IGFBP3 Pathway by Regulating GPX2

Radiotherapy remains a crucial treatment for esophageal squamous cell carcinoma (ESCC), although the development of radiation resistance and the occurrence of radiation-induced side effects pose significant clinical challenges. Selenium (Se) has obvious antitumor effects, but the sensitizing effect and mechanism of Se nanoparticles in ESCC radiotherapy remain to be determined. The aim of this study was to investigate which form of Se have superior sensitization of ESCC and to investigate how Se nanoparticles (LNT-SeNPs) can enhance the radiosensitivity of ESCC. Our findings indicate that LNT-SeNPs exhibit remarkable radiosensitizing activity with a higher safety index. These nanoparticles effectively inhibit cell growth, induce S-phase arrest, and promote apoptosis through increased reactive oxygen species (ROS) production. Furthermore, analysis via the GEO database revealed the correlation between the selenoprotein GPX2 and the radiosensitivity of esophageal cancer. Further investigations demonstrate that LNT-SeNPs suppress GPX2 expression, leading to apoptosis in ESCC cells via the p53/IGFBP3 signaling pathway. In conclusion, this study elucidates that LNT-SeNPs can enhance the effectiveness of radiotherapy for esophageal cancer, providing valuable insights into the potential use of Se-based drugs as adjunctive therapy. These findings pave the way for future clinical applications aimed at improving therapeutic outcomes in patients undergoing radiotherapy for ESCC.