Injury Site Specific Xenon Delivered by Platelet Membrane‐mimicking Hybrid Microbubbles to Protect Against Acute Kidney Injury via Inhibition of Cellular Senescence

Inhalation of xenon gas improved acute kidney injury (AKI). However, xenon can only be delivered through inhalation, which causes non-specific distribution and low bioavailability of xenon, thus limiting its clinical application. In this study, xenon was loaded into platelet membrane-mimicking hybrid microbubbles (Xe-Pla-MBs). In ischemia-reperfusion-induced AKI, intravenously injected Xe-Pla-MBs adhere to the endothelial injury site in the kidney. Xe-Pla-MBs were then disrupted by ultrasound, and xenon was released to the injured site. This release of xenon reduced ischemia-reperfusion-induced renal fibrosis and improved renal function, which were associated with decreased protein expression of cellular senescence markers p53 and p16, as well as reduced beta-galactosidase in renal tubular epithelial cells. Together, platelet membrane-mimicking hybrid microbubble-delivered xenon to the injured site protects against ischemia-reperfusion-induced AKI, which likely reduces renal senescence. Thus, the delivery of xenon by platelet membrane-mimicking hybrid microbubbles is a potential therapeutic approach for AKI. This article is protected by copyright. All rights reserved.