Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10901512 | Cancer Letters | 2016 | 14 Pages |
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.
Keywords
DOCEMSAElectrophoretic mobility shift assay (EMSA)MVBWFAUPLCqRT-PCRPACCURLPSPBSAFMEGFR3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecDNAMTTAnthocyanidinsFolic acidwithaferin Amultivesicular bodiesDrug deliverytumor necrosis factor-αChemotherapeutic drugsDocetaxelChemopreventive agentsVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)TNF-αlipopolysaccharidePhosphate-buffered salineSEMMicroRNAMiRNAScanning electron microscopyatomic force microscopyTumor-targetingquantitative reverse transcription-polymerase chain reactionPaclitaxelUltra-performance liquid chromatographyCurcuminEpidermal growth factor receptor
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Authors
Radha Munagala, Farrukh Aqil, Jeyaprakash Jeyabalan, Ramesh C. Gupta,