High yield, scalable and remotely drug-loaded neutrophil-derived extracellular vesicles (EVs) for anti-inflammation therapy.
High yield, scalable and remotely drug-loaded neutrophil-derived extracellular vesicles (EVs) for anti-inflammation therapy.
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DOI：
10.1016/j.biomaterials.2017.05.003
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发表时间：
2017-08
期刊：
影响因子：
14
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Gao J;Wang S;Wang Z
细胞外囊泡（EVs）是细胞自然分泌的纳米级膜性小囊，作为细胞间介质对生理过程和疾病发生起调节作用，因此有望成为新型的靶向递送治疗载体。然而，EVs的转化应用受到其成分不均一、产量低、药物装载效率低以及难以规模化生产等因素的制约。在此，我们报道一种利用氮气空化技术制备细胞外囊泡（NC - EVs）的策略，该技术可瞬间裂解中性粒细胞以形成纳米级膜囊泡。NC - EVs与自然分泌的细胞外囊泡（NS - EVs）类似，但所含的亚细胞器和核酸较少。与NS - EVs相比，NC - EVs的产量提高了16倍，且易于扩大规模以用于临床。为检验NC - EVs作为药物递送平台的有效性，我们通过pH梯度法将抗炎药物白皮杉醇远程装载到NC - EVs中。我们发现，装载了白皮杉醇的NC - EVs显著缓解了脂多糖（LPS）诱导的急性肺部炎症/损伤和败血症。我们的研究表明，氮气空化技术是一种从任何细胞类型高效制备细胞外囊泡的新方法，有望用于个性化纳米医学。
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
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影响因子：
17.1
作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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DOI：
10.1002/adma.201503323
发表时间：
2015-11-25
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Hu Q;Sun W;Qian C;Wang C;Bomba HN;Gu Z
通讯作者：
Gu Z