Zinc sulfide nanoparticles serve as gas slow-release bioreactors for H2S 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 H2S 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 H2S. In summary, our results indicate that ZnS NPs can be used as H2S slow-release bioreactors, offering a potentially innovative approach to treat ischemia-reperfusion injury caused by stroke. •ZnS-PEG NPs serve as gas slow-release bioreactors, showcasing stable and sustained H2S release while effectively removing RONS.•ZnS-PEG NPs reduce the oxidative injuries caused by OGD/R, promote the expression of p-AMPK, enhance microglia M2 polarization, decrease inflammatory factors and reduce cellular apoptosis.•ZnS-PEG NPs increase the proliferation and migration of endothelial cells, promoting the formation of new neurovascular units by regulating the expression of p-AKT.•ZnS-PEG NPs significantly reduce the infarct volume and restore the motor function of mice with MCAO/R.