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(AFGd-LDH)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~90%,surpassing CeO_(2)(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.