Background: Exosomes, widely recognized natural nanovesicles, represent one of the recently discovered modes of intercellular communication due to their ability to transmit crucial cellular information that can be engineered to have robust delivery and targeting capacity. MiR-142-3p, one of the upregulated microRNAs (miRNAs) in many types of breast cancer, activates the canonical Wnt signaling pathway and transactivates the miR-150 expression, and results in the hyperproliferation of cancer cells in vitro and mammary glands in vivo. Materials and methods: In this study, we exploited the exosomes isolated from bone marrow-derived mesenchymal stem cells (MSCs-Exo) to deliver LNA (locked nucleic acid)-modified anti-miR-142-3p oligonucleotides to suppress the expression level of miR-142-3p and miR-150 in 4T1 and TUBO breast cancer cell lines. Results: The in vitro results showed that the MSCs-Exo can efficiently deliver anti-miR-142-3p to reduce the miR-142-3p and miR-150 levels and increase the transcription of the regulatory target genes, APC and P2X7R. We also evaluated in vivo distribution of the MSCs-Exo in tumor-bearing mice. The in vivo result indicated that MSCs-Exo can penetrate the tumor site and are suitable nanovehicles to deliver the inhibitory oligonucleotides into the tumor tissues to downregulate the expression levels of miR-142-3p and miR-150. Conclusion: We showed that MSCs-derived exosomes could be used as a feasible nanovehicle to deliver drug molecules like LNA-anti-miR-142-3p in both in vitro and in vivo studies.

Purpose: Exosomes are small 30–100 nm vesicles secreted by various cell types. They are released by most cell types, indicating their important role in physiological and pathological processes, including signaling pathways, cell-to-cell communication, tumor progression, and molecule transferring. As natural nanovesicles, exosomes can be a good candidate for drug delivery due to low immunogenicity and ability to enter tissues and even cross the blood–brain barrier. In an effort to improve the efficiency of exosomes for targeted drug delivery with minimal effect on normal cells, we expressed ligands against HER2+ cells. Methods: To purify exosomes, transduced mesenchymal stromal cells were cultured to reach 80% confluency. Next, the cells were cultured in serum-free media for 48 hours and the supernatant was harvested to purify exosomes. These exosomes were then labeled with PKH67 and added to BT-474, SKBR3 (HER2+), and MDA-MB231 (HER2-), cell lines and their binding to HER2+ was evaluated by flow cytometry. Exosomes were loaded with doxorubicin and quantified using intrinsic fluorescence of doxorubicin at 594 nm. Results: Targeted exosomes were preferably uptaken by HER2+ cells. Therefore, untargeted exosomes showed lower binding to HER2+ cells compared to their targeted counterparts. MTT assay was performed to analyze cytotoxic effect of exo-DOX (exosome encapsulated with doxorubicin). Efficiency of exo-DOX and free DOX (doxorubicin) delivery with different concentrations, to the BT-474 cell line, was compared, and no significant difference was observed. Conclusion: Our results imply that targeted exosomes are preferentially uptaken by HER2+ cells relative to HER2- cells and have the potential to be used as an efficient drug delivery system.