Clinically used lipiodol as an effective radioenhancer

High atomic number (Z) element-based radiosensitizers have been widely reported for enhancing radiotherapeutic effect, while its limited tumor distribution and long-term safety are major limitations in clinics. In this study, we propose the clinically used lipiodol, a liquid radiological imaging agent with high iodine concentration, as a potential radiosensitizer. Compared to clinically approved high Z nanoradiosensitizer HfO2, lipiodol emulsion shows much better tumor spatial distribution and tumor inhibiting ability at in vivo level upon radiation treatment. In addition to primary tumor, lipiodol emulsion also exhibited efficient targetability and inhibition of lymph node metastasis with radiation treatment. Furthermore, the in vitro mechanism study indicates that lipiodol enhances radiotherapeutic effect by generating extra reactive oxygen species to cause DNA damage and cell death, irrespective of cancer type. Lastly, toxicity assessments demonstrate the safety of lipiodol for practical medical applications. This report provides scientific evidence supporting the century-old lipiodol as an effective liquid radiosensitizer ready for clinical implementation.