Zinc sulfide nanoparticles serve as gas slow-release bioreactors for HS therapy of ischemic stroke.

Stroke is one of the leading causes of death and disability in the world. Ischemic stroke causes overproduction of reactive oxygen/nitrogen species (RONS) after reperfusion, triggering inflammatory responses that further leads to cell damage. In order to develop novel neuroprotective materials, we synthesized zinc sulfide nanoparticles (ZnS NPs) to function as gas slow-release bioreactors, showcasing stable and sustained HS release while effectively removing RONS. In cultured cells, ZnS NPs can reduce the oxidative damage caused by oxygen-glucose deprivation and reoxygenation (OGD/R), promote the expression of p-AMPK, enhance microglia M2 polarization, decrease inflammatory factors and reduce neuronal apoptosis. Additionally, it increases the proliferation and migration of endothelial cells, promoting the formation of new neurovascular units by regulating the protein of p-AKT. In mice with ischemic stroke induced by middle cerebral artery occlusion/reperfusion (MCAO/R), ZnS NPs significantly reduce the infarct area and restore the mobility of mice owing to the slow release of HS. In summary, our results indicate that ZnS NPs can be used as HS slow-release bioreactors, offering a potentially innovative approach to treat ischemia-reperfusion injury caused by stroke.