Bovine milk-derived exosomes for drug delivery.
Bovine milk-derived exosomes for drug delivery.
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DOI：
10.1016/j.canlet.2015.10.020
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发表时间：
2016-02-01
期刊：
影响因子：
9.7
通讯作者：
Gupta RC
中科院分区：
文献类型：
--
作者：
Munagala R;Aqil F;Jeyabalan J;Gupta RC
外泌体是一种生物纳米囊泡，通过功能活性货物（如miRNA、mRNA、DNA和蛋白质）参与细胞间的通信。由于它们的纳米尺寸，外泌体被探索作为纳米器件用于开发新的治疗应用。然而，目前还没有大规模、安全、经济的外泌体生产方法。在这里，我们表明，牛奶可以作为外泌体的可扩展来源，可以作为化疗/化学预防剂的载体。与游离药物相比，载药外泌体在细胞培养研究和体内抗异种肺肿瘤移植中显示出更高的疗效。此外，肿瘤靶向配体，如叶酸，增加了癌细胞外泌体的靶向性，从而增强了肿瘤的减少。牛奶外泌体表现出跨物种耐受性，无不良免疫和炎症反应。因此，我们展示了乳外泌体的多功能性，它可以携带的货物和实现肿瘤靶向性的能力。这是首次发现一种具有生物相容性和成本效益的外泌体方法，以提高口服生物利用度，提高药物的疗效和安全性。
Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. However, bulk, safe and cost-effective production of exosomes is not available. Here, we show that bovine milk can serve as a scalable source of exosomes that can act as a carrier for chemotherapeutic/chemopreventive agents. Drug-loaded exosomes showed significantly higher efficacy compared to free drug in cell culture studies and against lung tumor xenografts in vivo. Moreover, tumor targeting ligands such as folate increased cancer-cell targeting of the exosomes resulting in enhanced tumor reduction. Milk exosomes exhibited cross-species tolerance with no adverse immune and inflammatory response. Thus, we show the versatility of milk exosomes with respect to the cargo it can carry and ability to achieve tumor targetability. This is the first report to identify a biocompatible and cost-effective means of exosomes to enhance oral bioavailability, improve efficacy and safety of drugs.