用于药物递送的牛乳源外泌体。

Bovine milk-derived exosomes for drug delivery.

作者信息

Munagala Radha, Aqil Farrukh, Jeyabalan Jeyaprakash, Gupta Ramesh C

机构信息

Department of Medicine, University of Louisville, Louisville, KY 40202.

James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.

出版信息

Cancer Lett. 2016 Feb 1;371(1):48-61. doi: 10.1016/j.canlet.2015.10.020. Epub 2015 Nov 18.

Abstract

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.

摘要

外泌体是一种生物纳米囊泡,通过功能活性物质(如微小RNA、信使核糖核酸、脱氧核糖核酸和蛋白质)参与细胞间通讯。由于其纳米尺寸,外泌体被探索作为纳米装置用于开发新的治疗应用。然而,目前尚无大量、安全且具有成本效益的外泌体生产方法。在此,我们表明牛乳可作为外泌体的可扩展来源,外泌体可作为化疗/化学预防剂的载体。在细胞培养研究以及体内针对肺肿瘤异种移植模型的实验中,载药外泌体显示出比游离药物显著更高的疗效。此外,诸如叶酸等肿瘤靶向配体可增强外泌体对癌细胞的靶向作用,从而增强肿瘤抑制效果。乳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在其所携带物质以及实现肿瘤靶向性方面的多功能性。这是首份鉴定出一种生物相容性好且具有成本效益的外泌体方法的报告,该方法可提高药物的口服生物利用度、改善疗效及安全性。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索