한빛사논문
Yohan Han 1, Yin Zhu 1, Hannah A Youngblood 2, Sultan Almuntashiri 1, Timothy W Jones 1, Xiaoyun Wang 1, Yutao Liu 2, Payaningal R Somanath 3, Duo Zhang 4
1Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, United States.
2Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, United States.
3Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, United States; Vascular Biology Center, Augusta University, Augusta, GA 30912, United States.
4Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, United States; Vascular Biology Center, Augusta University, Augusta, GA 30912, United States; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States.
Corresponding Author: Duo Zhang
Abstract
Small extracellular vesicles (sEVs) are a group of cell-secreted nanovesicles with a diameter up to 200 nm. A growing number of studies have indicated that sEVs can reflect the pathogenesis of human diseases and mediate intercellular communications. Recently, sEV research has drastically increased due to their drug delivery property. However, a comprehensive method of delivering exogenous small RNAs-loaded sEVs through nebulization has not been reported. The methodology is complicated by uncertainty regarding the integrity of sEVs after nebulization, the delivery efficiency of aerosolized sEVs, their deposition in the lungs/cells, etc. This study demonstrates that sEVs can be delivered to murine lungs through a vibrating mesh nebulizer (VMN). In vivo sEV tracking indicated that inhaled sEVs were distributed exclusively in the lung and localized primarily in lung macrophages and airway epithelial cells. Additionally, sEVs loaded with small RNAs were successfully delivered into the lungs. The administration of siMyd88-loaded sEVs through inhalation reduced lipopolysaccharide (LPS)-induced lung injury in mice, supporting an application of this nebulization methodology to deliver functional small RNAs. Collectively, our study proposes a novel method of sEVs-mediated small RNA delivery into the murine lung through nebulization and presents a potential sEV-based therapeutic strategy for human lung diseases.
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