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

Abstract

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.