Radioprotective nanomedicines: New horizons in mitigating radiation-induced tissue injury

Background Ionizing radiation remains indispensable in cancer therapy, diagnostics, and industrial and space applications, yet radiation-induced normal tissue injury continues to limit therapeutic efficacy and long-term patient outcomes. Conventional radioprotectors have shown restricted clinical success due to poor pharmacokinetics, systemic toxicity, and lack of tissue selectivity, underscoring the need for fundamentally new protective strategies. Methods This review synthesizes recent advances in radioprotective nanomedicines by integrating evidence from radiation biology, nanomaterials science, preclinical modeling, and regulatory science. Emphasis is placed on mechanistic classification, translational readiness, safety, pharmacokinetics, and clinical feasibility rather than descriptive material catalogs. Key findings The radioprotectors of nanomedicine allow flexible and localized protection at the systems level by catalytic redox modulation, endothelial/immune targeting, transfection of genes and enzymes, and local depot. New trends that concern ferroptosis inhibition, biomarker-directed precision radioprotection, and radiation-activated smart nanoplatforms eliminate the weaknesses that have affected classical agents. Nonetheless, some of the bottlenecks are reproducibility, long-term safety, manufacturability, and regulatory alignment. Conclusion Radioprotective nanomedicines offer a realistic path toward selective normal tissue protection without compromising tumor control. With standardized evaluation frameworks and disciplined translational strategies, these platforms have considerable translational potential; however, further preclinical validation, clinical evaluation, and regulatory advancement is required before widespread clinical implementation.