Targeted strategy by curcumin and tideglusib biomimetic nano-systems alleviates oxidative stress and inflammation under ischemic stroke

Ischemic stroke represents one of the leading causes of disability and death worldwide. Neuroprotection aimed at mitigating oxidative stress and inflammation is crucial for improving the prognosis of patients. However, the inadequate accumulation of drugs at the ischemic site significantly restricts their clinical efficacy. We found that platelet membrane (PLTM)-biomimetic nanosystems loaded with curcumin (Cur@PLTM) and tideglusib (Tid@PLTM) actively targeted the ischemic brain and facilitated transcytosis into the ischemic parenchyma via caveolin-dependent transcytosis, mimicking the recruitment of platelets in damaged cerebral vessels. This represented the first application of tideglusib nanoformulations in treating ischemic stroke, further demonstrating that the therapeutic effects were associated with M2 microglia regulation. Additionally, Cur@PLTM and Tid@PLTM synergistically scavenged reactive oxygen species (ROS) and promoted the secretion of neuroprotective cytokines via redox and cellular regulatory mechanisms to mitigate ischemia/reperfusion (I/R) injury. Overall, this platelet membrane-biomimetic nanosystem offers a prospective strategy for targeted brain delivery and combined treatment through antioxidative and anti-inflammatory approaches against ischemic stroke. Tid nanoformulations treat ischemic stroke and regulate M2-type microglia. Both Cur and Tid in PLTM-NPs synergistically regulate oxidative stress and inflammation. Tids have strong potential to scavenge ROS in microglia and brain endothelial cells. Caveolin-dependent transcytosis of PLTM-NPs facilitates their ability to cross the BBB.

缺血性脑卒中（ischemic stroke）是全球范围内导致残疾与死亡的主要病因之一。旨在减轻氧化应激与炎症反应的神经保护策略，对改善患者预后至关重要。然而，药物在缺血灶内的蓄积量不足，极大限制了其临床疗效。
本研究发现，负载姜黄素（curcumin，Cur）的血小板膜（platelet membrane，PLTM）仿生纳米系统（Cur@PLTM）与负载 tideglusib（Tid）的血小板膜仿生纳米系统（Tid@PLTM），可主动靶向缺血脑组织，并通过依赖小窝蛋白（caveolin）的转胞吞作用（transcytosis），促进药物穿越进入缺血脑实质，模拟血小板在受损脑血管中的募集过程。这是 tideglusib 纳米制剂首次应用于缺血性脑卒中的治疗，进一步证实其治疗效应与M2型小胶质细胞调控相关。
此外，Cur@PLTM与Tid@PLTM可通过氧化还原与细胞调控机制，协同清除活性氧（reactive oxygen species，ROS）并促进神经保护细胞因子的分泌，以减轻缺血再灌注（ischemia/reperfusion，I/R）损伤。
综上，该血小板膜仿生纳米系统为通过抗氧化与抗炎策略实现靶向脑递送及联合治疗缺血性脑卒中提供了极具前景的方案。
Tideglusib纳米制剂可用于治疗缺血性脑卒中并调控M2型小胶质细胞。
血小板膜纳米颗粒（PLTM-NPs）中的姜黄素与Tideglusib可协同调控氧化应激与炎症反应。
Tideglusib在小胶质细胞与脑内皮细胞中具备清除活性氧的巨大潜力。
血小板膜纳米颗粒（PLTM-NPs）依赖小窝蛋白的转胞吞作用，可增强其穿越血脑屏障（blood-brain barrier，BBB）的能力。