Coordination chemistry enabled in vivo radioprotective material for alleviating acute radiation syndrome

The most life-threatening injury induced by radiation is acute radiation syndrome (ARS), which is featured by damage to the hematopoietic system and vital organs. However, most efforts focus on scavenging radiation-induced reactive oxygen species (ROS). Designing more direct strategies like in vivo radiation shielding remains in its infancy. Here we propose a supramolecularly orchestrated high-atomic number ( Z ) strategy, designing a bismuth-coordinated melanin-based radioprotectant for achieving physical shielding in vivo. The supramolecular coordination of bismuth endows the biomaterial with superior photon-shielding capacity, while maintaining melanin’s inherent ROS-scavenging function. In animal experiments, this strategy effectively alleviated ARS, maintained normal hematopoietic function and protected the gastrointestinal tract, resulting in improved long-term survival from 20% to 60%. This radioprotectant also exhibited excellent biocompatibility and metabolism. High- Z nanomaterials for in vivo applications utilize supramolecular coordination to combine metals with natural macromolecules, offering an effective strategy for developing radioprotectants. Moreover, Bi-coordinated poly L -3,4-dihydroxyphenylalanine melanin outperforms its polydopamine analogue, revealing that side-chain subtleties dictate radioprotective potency.