期刊
CANCER LETTERS
卷 371, 期 1, 页码 48-61出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.10.020
关键词
Milk-derived exosomes; Drug delivery; Tumor-targeting; Chemotherapeutic drugs; Chemopreventive agents
类别
资金
- USPHS [CA-118114, CA-125152, R41-CA-189517]
- Kentucky Lung Cancer Research Program
- Agnes Brown Duggan Endowment
- Helmsley Funds
- NATIONAL CANCER INSTITUTE [R41CA189517, R01CA125152, R01CA118114] Funding Source: NIH RePORTER
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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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