Res@LDH: A Novel Nanohybrid Therapeutic for Ischemia–Reperfusion Injury with Dual Reactive Oxygen Species Scavenging Efficiency

Abstract

Ischemic stroke poses a global health challenge, necessitating effective therapeutic interventions given the limited time window for thrombolytic therapy. Here, we present Res@LDH, a novel nanohybrid therapeutic agent boasting a dual reactive oxygen species scavenging efficiency of approximately 90%. Comprising Ge-containing layered double hydroxide nanosheets (Ge-LDH) as a drug nanocarrier and resveratrol as a neuroprotective agent, Res@LDH demonstrates enhanced permeability across the blood–brain barrier, ensuring high biocompatibility and stability. We explored the potential of Res@LDH in mitigating oxidative stress injury induced by middle cerebral artery occlusion and reperfusion in mice, as well as H2O2-induced cytotoxicity in HT22 cells. Our experiments unveil Res@LDH’s capacity to ameliorate neurological deficits, reduce the infarction volume, mitigate blood–brain barrier disruption, exhibit a robust antioxidant activity, and dampen the release of proinflammatory cytokines. Moreover, Res@LDH treatment markedly attenuates microglial and astrocytic activation. Leveraging a pioneering synthetic approach harnessing Ge-LDH and resveratrol, Res@LDH emerges as a promising strategy for addressing ischemia–reperfusion injury, offering a concise solution to current therapeutic challenges.