Gao Jin, Wang Sihan, Wang Zhenjia
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA.
Biomaterials. 2017 Aug;135:62-73. doi: 10.1016/j.biomaterials.2017.05.003. Epub 2017 May 3.
Extracellular vesicles (EVs) are nanoscale membrane-formed compartments naturally secreted from cells, which are intercellular mediators regulating physiology and pathogenesis, therefore they could be a novel therapeutic carrier for targeted delivery. However, the translation of EVs is hindered by the heterogeneous composition, low yield, inefficient drug loading and unlikely scalability. Here we report a strategy to generate EVs using nitrogen cavitation (NC-EVs) that instantly disrupts neutrophils to form nanosized membrane vesicles. NC-EVs are similar to naturally secreted EVs (NS-EVs), but contain less subcellular organelles and nuclear acids. The production of NC-EVs was increased by 16 folds and is easy to scale up for clinical use compared to NS-EVs. To examine the usefulness of NC-EVs as a drug delivery platform, piceatannol (an anti-inflammation drug) was remotely loaded in NC-EVs via the pH gradient. We found that piceatannol-loaded NC-EVs dramatically alleviated acute lung inflammation/injury and sepsis induced by lipopolysaccharide (LPS). Our studies reveal that nitrogen cavitation is a novel approach to efficiently generate EVs from any cell type and could be exploited for personalized nanomedicine.
细胞外囊泡（EVs）是细胞自然分泌的纳米级膜性小室，是调节生理和发病机制的细胞间介质，因此它们可能成为一种新型的靶向递送治疗载体。然而，EVs的转化受到其成分异质性、产量低、药物负载效率低以及难以规模化生产的阻碍。在此，我们报道了一种利用氮气空化作用生成EVs的策略（NC-EVs），该方法能瞬间破坏中性粒细胞以形成纳米级膜囊泡。NC-EVs与天然分泌的EVs（NS-EVs）相似，但所含亚细胞器和核酸较少。与NS-EVs相比，NC-EVs的产量提高了16倍，且易于扩大规模用于临床。为了检验NC-EVs作为药物递送平台的效用，通过pH梯度将白藜芦醇（一种抗炎药物）远程负载到NC-EVs中。我们发现负载白藜芦醇的NC-EVs能显著减轻脂多糖（LPS）诱导的急性肺炎症/损伤和败血症。我们的研究表明，氮气空化是一种从任何细胞类型高效生成EVs的新方法，可用于个性化纳米医学。
