Abstract
Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.