RVG-peptide-camouflaged iron-coordinated engineered polydopamine nanoenzyme with ROS scavenging and inhibiting inflammatory response for ischemic stroke therapy.

Stroke is one of the most common causes of death and disability. In addition, most neuroprotective agents fail to rescue neurons from cerebral ischemic insults due to their poor ability to penetrate the blood-brain barrier (BBB). Here, the tailored engineered nanoenzyme has been successfully synthesized by coordination-driven co-assembly of dopamine (DA) and iron ion (Fe3+), which is subsequently camouflaged by neuron-specific rabies viral glycoprotein (RVG) peptide to scavenge reactive oxygen species (ROS) and inhibit inflammatory response in damaged neuron for the efficient therapy of ischemic stroke. The resulting nanoenzyme with good biocompatibility, core-shell structure, and suitable diameter can nondestructively cross the BBB and then internalize into the damaged neuron through the camouflaging and homologous targeted strategy of neuron-specific RVG peptide. After intravenous injection into transient middle cerebral artery occlusion (tMCAO) mouse models, nanoenzyme exerted a significant neuroprotective effect, resulting in a 50 % reduction in neurological scores and an approximate 33 % decrease in cerebral infarction volume. Interestingly, such nanoenzyme can eliminate free radicals, reduce neuroinflammation, enhance BBB integrity, improve mitochondrial function, and inhibit neuronal ferroptosis. Taken together, this well-designed nanoenzyme with its excellent biocompatibility and well-understood mechanisms holds promise a robust therapy for ischemic stroke.