Engineering iron oxide nanoparticles for enhanced radiosensitization.

Iron oxide nanoparticles (IONPs) have recently demonstrated considerable potential for enhancing the effectiveness of radiotherapy through radiosensitization. In this study, the radiosensitizing performance of commercial IONPs (Sinerem® and Endorem®) was compared with that of synthesized carboxylated IONPs with different core sizes (5-12 nm) in A549 lung carcinoma cells. A comprehensive evaluation of key biological mechanisms, including cellular internalization, reactive oxygen species (ROS) generation, lysosomal degradation and thioredoxin reductase (TrxR) inhibition, was conducted. Carboxylated IONPs, particularly those with a 7 nm core diameter, exhibited superior radiosensitizing effects, associated with enhanced cellular uptake and substantial TrxR inhibition. By contrast, commercial IONPs exhibited poor internalization and minimal radiosensitizing capacity. Interestingly, no detectable increase in basal ROS levels was found across the different formulations under the tested conditions. Instead, the stronger radiosensitizing response observed with carboxylated IONPs was associated with higher TrxR inhibition and redox imbalance. These findings suggest that sustained ROS overproduction induced by IONP exposure alone is unlikely to be the main driver of the observed effect. These results highlight how nanoparticle size, surface chemistry and intracellular degradation are critical parameters to consider in the development of efficient radiosensitizing agents.