Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
The Institute for Translational Nanomedicine, Shanghai East Hospital, Shanghai, 200120, China.
J Nanobiotechnology. 2022 Jun 25;20(1):299. doi: 10.1186/s12951-022-01495-6.
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.
创伤性脑损伤 (TBI) 是全球范围内导致残疾和死亡的一个原因，但目前针对这种情况尚无特定的治疗方法。受伤大脑中过量活性氧 (ROS) 的释放会导致一系列病理变化；因此，消除 ROS 可能是一种有潜力的治疗策略。在此，我们通过绿色仿生化学合成了胰岛素孵育的超小钯 (Pd@胰岛素) 簇。这些直径为 3.2nm 的 Pd@胰岛素簇表现出显著的多种 ROS 清除能力，这已通过理论计算得到证实。Pd@胰岛素可通过肾脏-尿液代谢迅速排出，并且在体内长时间治疗后诱导出可忽略的不良反应。在 TBI 小鼠模型中，静脉注射的 Pd@胰岛素簇在损伤皮层中聚集，有效抑制了过量 ROS 的产生，并显著改善了运动功能、认知和空间记忆。我们发现，Pd@胰岛素簇的积极治疗效果主要归因于其 ROS 清除能力，因为它抑制了过度的神经炎症、减少了细胞凋亡并防止了神经元丢失。因此，Pd@胰岛素簇有效消除 ROS 的能力，以及其简单的结构、易于合成、低毒性和快速代谢可能有助于其在 TBI 治疗中的临床转化。
