Recent Progress in the Development of Metal-Based Radiosensitizations for Cancer Therapy: A Review

Abstract

Radiotherapy (RT) remains an indispensable means in cancer treatment; however, its therapeutic efficacy is often limited by tumor radioresistance and side effect of damage to healthy tissue. The advances in nanotechnology have propelled metal radiosensitizers to forefront of precision medicine. These metal-based radiosensitizations enhance RT efficacy through multifaceted mechanisms of physical dose amplification, chemical catalysis, and biological modulation. Compared to conventional way by employing high atomic number (high-Z) metal materials to enhance energy deposition, emerging strategies such as X-ray induced radiodynamic therapy (X-RDT) and Cerenkov radiation activated photodynamics therapy (CR-PDT), have been developed to synergize RT with deep-tumor reactive oxygen species (ROS) generation under lower radiation dose. In this review, we highlight recent progress in metal-based radiosensitization for cancer therapy, discuss key challenges hindering clinical translation, and emphasize innovations in material design, combinatorial therapies, and clinical oncology. Collectively, these advances may unlock the full potential of metal-based radiosensitizers, paving the way for curative RT with minimal damage to normal tissues.