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Article

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

1
Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, CEI UAM+CSIC, 28049 Madrid, Spain
2
Laboratory of Functional Foods, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, CEI UAM+CSIC, 28049 Madrid, Spain
3
Laboratory of Cardiometabolic Nutrition, Instituto Madrileño de Estudios Avanzados (IMDEA)-Alimentación, CEI UAM+CSIC, 28049 Madrid, Spain
4
Department of Biochemistry-Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain
5
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28034 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Adela Ramírez-Torres and Jesús Osada
Int. J. Mol. Sci. 2021, 22(3), 1105; https://doi.org/10.3390/ijms22031105
Received: 29 December 2020 / Revised: 15 January 2021 / Accepted: 19 January 2021 / Published: 22 January 2021
(This article belongs to the Special Issue Nutrition Genomics 2.0)
MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the possibility of successfully exerting a biological function in distant target cells. Strategies aimed at enhancing the therapeutic potential of miRNAs include the development of efficient, tissue-specific and nonimmunogenic delivery methods. Since miRNAs were discovered to be naturally transported within exosomes, a type of extracellular vesicle that confers protection against RNase degradation and increases miRNA stability have been proposed as ideal delivery vehicles for miRNA-based therapy. Although research in this field has grown rapidly in the last few years, a standard, reproducible and cost-effective protocol for exosome isolation and extracellular RNA delivery is lacking. We aimed to evaluate the use of milk-derived extracellular vesicles as vehicles for extracellular RNA drug delivery. With this purpose, exosomes were isolated from raw bovine milk, combining ultracentrifugation and size exclusion chromatography (SEC) methodology. Isolated exosomes were then loaded with exogenous hsa-miR148a-3p, a highly expressed miRNA in milk exosomes. The suitability of exosomes as delivery vehicles for extracellular RNAs was tested by evaluating the absorption of miR-148a-3p in hepatic (HepG2) and intestinal (Caco-2) cell lines. The potential exertion of a biological effect by miR-148a-3p was assessed by gene expression analysis, using microarrays. Results support that bovine milk is a cost-effective source of exosomes which can be used as nanocarriers of functional miRNAs with a potential use in RNA-based therapy. In addition, we show here that a combination of ultracentrifugation and SEC technics improve exosome enrichment, purity, and integrity for subsequent use. View Full-Text
Keywords: extracellular vesicles; miRNAs; exosomes; bovine milk; size exclusion chromatography extracellular vesicles; miRNAs; exosomes; bovine milk; size exclusion chromatography
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MDPI and ACS Style

del Pozo-Acebo, L.; López de las Hazas, M.-C.; Tomé-Carneiro, J.; Gil-Cabrerizo, P.; San-Cristobal, R.; Busto, R.; García-Ruiz, A.; Dávalos, A. Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy. Int. J. Mol. Sci. 2021, 22, 1105. https://doi.org/10.3390/ijms22031105

AMA Style

del Pozo-Acebo L, López de las Hazas M-C, Tomé-Carneiro J, Gil-Cabrerizo P, San-Cristobal R, Busto R, García-Ruiz A, Dávalos A. Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy. International Journal of Molecular Sciences. 2021; 22(3):1105. https://doi.org/10.3390/ijms22031105

Chicago/Turabian Style

del Pozo-Acebo, Lorena, M-C López de las Hazas, Joao Tomé-Carneiro, Paula Gil-Cabrerizo, Rodrigo San-Cristobal, Rebeca Busto, Almudena García-Ruiz, and Alberto Dávalos. 2021. "Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy" International Journal of Molecular Sciences 22, no. 3: 1105. https://doi.org/10.3390/ijms22031105

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