Targeted alleviation of ischemic stroke reperfusion via atorvastatin-ferritin Gd-layered double hydroxide

In acute ischemic stroke therapy, potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species (ROS) during ischemic reperfusion. Herein, a novel 2D neuroprotective agent (AFGdLDH) is reported, comprising Gd-containing layered double hydroxide nanosheets (Gd-LDH, as a drug nanocarrier/MRI contrast agent), atorvastatin (ATO, as a neuroprotective drug) and the ferritin heavy subunit (FTH, as a blood brain barrier transport agent). Experiments revealed AFGd-LDH to possess outstanding antioxidant activity, neuroprotective properties, blood-brain barrier transit properties, and biocompatibility. In vitro studies demonstrated the ROS scavenging efficiency of AFGd-LDH to be similar to 90%, surpassing CeO2 (50%, a ROS scavenger) and edaravone (52%, a clinical neuroprotective drug). Ischemia-reperfusion model studies in mice showed AFGd-LDH could dramatically decrease apoptosis induced by reperfusion, reducing the infarct area by 67% and lowering the neurological deficit score from 3.2 to 0.9. AFGd-LDH also offered outstanding MRI performance, thus enabling simultaneous imaging and ischemia reperfusion therapy.

Automated summary

In acute ischemic stroke therapy, a novel neuroprotective agent called AFGdLDH comprising Gd-containing layered double hydroxide nanosheets, atorvastatin, and ferritin heavy subunit has been developed. This agent exhibits outstanding antioxidant activity and neuroprotective properties, reducing neural injuries caused by reactive oxygen species during ischemic reperfusion.