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      Bovine milk-derived exosomes for drug delivery

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          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.

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          Author and article information

          Journal
          7600053
          2780
          Cancer Lett
          Cancer Lett.
          Cancer letters
          0304-3835
          1872-7980
          5 December 2015
          18 November 2015
          1 February 2016
          01 February 2017
          : 371
          : 1
          : 48-61
          Affiliations
          [1 ]Department of Medicine, University of Louisville, Louisville, KY 40202
          [2 ]James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202
          [3 ]Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202
          Author notes
          [# ]Corresponding author: Ramesh C. Gupta, Delia Baxter II, Room 304E, University of Louisville, 580 S. Preston Street, Louisville, KY 40202. rcgupta@ 123456louisville.edu ; Tel: 502-852-3682.
          Article
          PMC4706492 PMC4706492 4706492 nihpa739340
          10.1016/j.canlet.2015.10.020
          4706492
          26604130
          1f21d52c-9c98-4280-8d7e-7fd14d732123
          History
          Categories
          Article

          drug delivery,chemotherapeutic drugs,tumor-targeting,Milk-derived exosomes,chemopreventive agents

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