Potential applications of metal-based nanomaterials in tumor radiotherapy: from x-ray to particle therapies

The integration of radiotherapy (RT) with nanotechnology has emerged as a promising strategy for enhancing cancer treatment efficacy. While RT remains a cornerstone in oncology, challenges such as tumor hypoxia, radioresistance, and off-target toxicity limit its therapeutic potential. Metal-based nanoparticles (MNPs), including gold (Au), hafnium (Hf), bismuth (Bi), gadolinium (Gd), and iron oxide, have gained increasing attention for their ability to enhance radiation dose deposition, amplify reactive oxygen species (ROS) production, and modulate the tumor microenvironment (TME), thereby improving RT outcomes. In parallel, MNPs have demonstrated potential in advanced particle therapies, such as proton and heavy-ion treatments, where their high atomic number properties optimize dose distribution and linear energy transfer (LET) effects. Several MNPs, including NBTXR3 (hafnium oxide) and AGuIX (gadolinium-based), have advanced to clinical trials. They have shown improved radiosensitization and immune activation. This review examines the intersection of MNPs and RT, focusing on how they increase radiation effects on tumors. It covers recent progress, main challenges in clinical use, and ways to improve MNP-based RT. Finally, we discuss the future prospects of integrating MNPs into precision oncology, highlighting the need for standardized evaluation protocols and interdisciplinary collaboration to fully realize their clinical potential.