Bovine milk-derived exosomes for drug delivery

被引:854
作者
Munagala, Radha [1 ,2 ]
Aqil, Farrukh [1 ,2 ]
Jeyabalan, Jeyaprakash [2 ]
Gupta, Ramesh C. [2 ,3 ]
机构
[1] Univ Louisville, Dept Med, Louisville, KY 40202 USA
[2] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA
[3] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40202 USA
关键词
Milk-derived exosomes; Drug delivery; Tumor-targeting; Chemotherapeutic drugs; Chemopreventive agents; IMMUNE-RELATED MICRORNAS; EXTRACELLULAR VESICLES; CANCER-THERAPY; BREAST-MILK; IN-VIVO; SYSTEM; CELLS; RNA; NANOTECHNOLOGY; MICROVESICLES;
D O I
10.1016/j.canlet.2015.10.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:48 / 61
页数:14
相关论文
共 51 条
[1]
Exosomes with immune modulatory features are present in human breast milk [J].
Admyre, Charlotte ;
Johansson, Sara M. ;
Qazi, Khaleda Rahman ;
Filen, Jan-Jonas ;
Lahesmaa, Riitta ;
Norman, Mikael ;
Neve, Etienne P. A. ;
Scheynius, Annika ;
Gabrielsson, Susanne .
JOURNAL OF IMMUNOLOGY, 2007, 179 (03) :1969-1978
[2]
Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models [J].
Arntz, Onno J. ;
Pieters, Bartijn C. H. ;
Oliveira, Marina C. ;
Broeren, Mathijs G. A. ;
Bennink, Miranda B. ;
de Vries, Marieke ;
van Lent, Peter L. E. M. ;
Koenders, Marije I. ;
van den Berg, Wim B. ;
van der Kraan, Peter M. ;
van de Loo, Fons A. J. .
MOLECULAR NUTRITION & FOOD RESEARCH, 2015, 59 (09) :1701-1712
[3]
Syndecan-syntenin-ALIX regulates the biogenesis of exosomes [J].
Baietti, Maria Francesca ;
Zhang, Zhe ;
Mortier, Eva ;
Melchior, Aurelie ;
Degeest, Gisele ;
Geeraerts, Annelies ;
Ivarsson, Ylva ;
Depoortere, Fabienne ;
Coomans, Christien ;
Vermeiren, Elke ;
Zimmermann, Pascale ;
David, Guido .
NATURE CELL BIOLOGY, 2012, 14 (07) :677-685
[4]
Bamrungsap S, 2012, NANOMEDICINE-UK, V7, P1253, DOI [10.2217/nnm.12.87, 10.2217/NNM.12.87]
[5]
Development and In Vitro-In Vivo Evaluation of Polymeric Implants for Continuous Systemic Delivery of Curcumin [J].
Bansal, Shyam S. ;
Vadhanam, Manicka V. ;
Gupta, Ramesh C. .
PHARMACEUTICAL RESEARCH, 2011, 28 (05) :1121-1130
[6]
Doxil® - The first FDA-approved nano-drug: Lessons learned [J].
Barenholz, Yechezkel .
JOURNAL OF CONTROLLED RELEASE, 2012, 160 (02) :117-134
[7]
Identification of a Conserved Glycan Signature for Microvesicles [J].
Batista, Bianca S. ;
Eng, William S. ;
Pilobello, Kanoelani T. ;
Hendricks-Munoz, Karen D. ;
Mahal, Lara K. .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (10) :4624-4633
[8]
Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release [J].
Chen, Shuyi ;
Zhao, Xianrui ;
Chen, Jingyi ;
Chen, Jin ;
Kuznetsova, Larisa ;
Wong, Stanislaus S. ;
Ojima, Iwao .
BIOCONJUGATE CHEMISTRY, 2010, 21 (05) :979-987
[9]
Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer [J].
Ciruelos, Eva ;
Jackisch, Christian .
EXPERT REVIEW OF ANTICANCER THERAPY, 2014, 14 (05) :511-521
[10]
Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications [J].
Corrado, Chiara ;
Raimondo, Stefania ;
Chiesi, Antonio ;
Ciccia, Francesco ;
De Leo, Giacomo ;
Alessandro, Riccardo .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (03) :5338-5366