Reactive oxygen species-scavenging nanozymes for radioprotection of healthy tissues

• Radiotherapy often causes unavoidable collateral damage to healthy tissues. • Excessive ROS generation is a key mechanism in radiation-induced injury. • Nanozymes effectively scavenge ROS with multifunctional catalytic activity. • ROS-scavenging nanozymes offer promising strategies for radioprotection. Radiation therapy is widely used in tumor treatment, but it inevitably induces collateral damage to adjacent healthy tissues. Reactive oxygen species (ROS) serve as central drivers of radiation-induced normal tissue injury (RINTD), initiating and propagating pathological processes such as oxidative stress, inflammatory amplification, cell death, and compromised tissue regeneration. Therefore, scavenging ROS has emerged as a promising strategy to mitigate RINTD. In this context, ROS-scavenging nanozymes—nanomaterials with enzyme-like catalytic activities—have recently gained significant interest owing to their tunable catalytic performance and programmable structures that enable efficient and multifunctional ROS elimination. This review delineates the pathogenic mechanisms of ROS in RINTD and systematically summarizes the working principles, material design strategies, and recent applications of nanozymes for tissue radioprotection. We also discuss persistent challenges and future directions, with the goal of inspiring the rational design of advanced nanozymes and accelerating their clinical translation in tissue radioprotection.