Radiotherapy meets anticancer metallodrugs

Abstract Combined radiotherapy and chemotherapy remain central to cancer treatment, with metallodrugs – most notably platinum agents – playing indispensable roles in clinical regimens. However, systemic toxicity and limited tumor selectivity continue to constrain their optimal integration with radiotherapy. Recent advances in radiation precision and metal chemistry are reshaping this landscape, giving rise to strategies in which radiotherapy and anticancer metallodrugs no longer act merely in combination, but intersect at the molecular level. Ionizing radiation generates highly reactive chemical species that can be harnessed to activate, modulate, or amplify the function of metallodrugs within irradiated tissues. Across platinum prodrugs, non-platinum metal complexes, and high-Z metal materials, radiation energy is increasingly exploited to achieve spatially confined cytotoxicity, immune modulation, and synergistic tumor control. Notably, radiometal-based drugs integrate radiochemistry with metal coordination chemistry, positioning themselves at the intersection of radiotherapy and metallodrug therapy, where they are already playing an increasingly important role in clinical oncology.