Recent progress on the application of heavy metal nanoparticles in radiotherapy sensitization

Radiotherapy remains one of the cornerstone modalities in the clinical treatment of malignant tumors. However, the intrinsic radioresistance of tumor cells—particularly hypoxia-induced tolerance within the tumor microenvironment—significantly limits therapeutic efficacy. With advancements in nanomedicine, high-atomic-number (high-Z) heavy metal-based nanoparticles (GNPs) have demonstrated great potential in overcoming tumor radioresistance due to their unique physical, chemical, and biological properties. This review systematically summarizes recent progress on high-Z metal-based nanoparticles (e.g., gold, gadolinium, bismuth, and iridium), their nanoscale metal–organic frameworks (nMOFs, e.g., hafnium-based and zirconium-based systems), and metal-doped nanomaterials developed for enhancing radiotherapy outcomes. We highlight the mechanisms by which these materials achieve radiosensitization, including enhancement of local radiation energy deposition, catalytic generation of reactive oxygen species (ROS), modulation of the tumor microenvironment, and activation of immunogenic cell death (ICD). The advantages of high-Z metal-based nMOFs in drug delivery and catalytic performance are also discussed. Finally, we analyze the major translational challenges, including biodistribution and long-term toxicity, and propose material engineering strategies and future research directions toward integrated theranostic applications.