An eNOS-like nanomaterial for specific reversal of cerebral ischemia-reperfusion injury

The protective role of NO has been widely verified in cerebrovascular diseases. However, the beneficial effects of NO depend on its concentration and reactive oxygen species (ROS) level, which makes current NO donors face great difficulties in treating cerebral ischemia-reperfusion injury (CIRI). Here, a tailored MoS2-based NO donor (MSNO) was constructed with defect-rich MoS2, in which the abundant S edge sites in the defects form -SNO, and the Mo sites can also bind NO to form Mo-NO. Combined with MSNO's own strong ability to eliminate ROS, MSNO could provide pure NO at suitable concentrations like eNOS and avoid the generation of highly toxic ONOO-. After intravenous injection, MSNO with suitable nano-size could penetrate the blood-brain barrier of ischemia-reperfusion injured brain tissue, and effectively treat CIRI through multiple effects: inhibiting calcium overload, alleviating mitochondrial damage and endoplasmic reticulum stress, and inhibiting the inflammatory storm. Nitric oxide in known to have a protective effect in cerebrovascular disease. Here, the authors report on MoS2 an eNOS mimetic which releases NO while avoiding toxic ONOO- production, demonstrating therapeutic effects in inhibiting several damage pathways in cerebral ischemia-reperfusion injury.