Injury Site Specific Xenon Delivered by Platelet Membrane-Mimicking Hybrid Microbubbles to Protect Against Acute Kidney Injury via Inhibition of Cellular Senescence
Injury Site Specific Xenon Delivered by Platelet Membrane-Mimicking Hybrid Microbubbles to Protect Against Acute Kidney Injury via Inhibition of Cellular Senescence
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DOI：
10.1002/adhm.202203359
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发表时间：
2023-04-14
影响因子：
10
通讯作者：
Yao，Weifeng
中科院分区：
文献类型：
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作者：
Yang，Jing;Chen，Chaojin;Yao，Weifeng
吸入氙气可改善急性肾损伤（阿基）。然而，氙气只能通过吸入给药，这导致氙气的非特异性分布和低生物利用度，从而限制了其临床应用。在这项研究中，氙被加载到血小板膜模拟混合微泡（AMB-Pla-MB）中。在缺血-再灌注诱导的阿基中，静脉注射的APLa-MB粘附在肾脏的内皮损伤部位。然后用超声波破坏骨-Pla-MB，并将氙气释放到受伤部位。氙的释放减少了缺血再灌注诱导的肾纤维化并改善了肾功能，这与细胞衰老标志物p53和p16的蛋白表达降低以及肾小管上皮细胞中β-半乳糖苷酶的降低有关。总之，血小板膜模拟混合微泡将氙递送到损伤部位可防止缺血再灌注诱导的阿基，这可能会减少肾脏衰老。因此，通过血小板膜模拟混合微泡递送氙是阿基的潜在治疗方法。
Inhalation of xenon gas improves 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 is 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 are then disrupted by ultrasound, and xenon is released to the injured site. This release of xenon reduced ischemia‐reperfusion‐induced renal fibrosis and improved renal function, which are 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 injred 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.