Targeted Exosomes Deliver Antitumor Therapy to Breast Cancer Cells

Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack of appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that are secreted by a variety of cell types and tissues.

Here, Tokyo Medical University researchers show that exosomes can efficiently deliver microRNA (miRNA) to epidermal growth factor receptor (EGFR)-expressing breast cancer cells. Targeting was achieved by engineering the donor cells to express the transmembrane domain of platelet-derived growth factor receptor fused to the GE11 peptide. Intravenously injected exosomes delivered let-7a miRNA to EGFR-expressing xenograft breast cancer tissue in RAG2-/- mice. These results suggest that exosomes can be used therapeutically to target EGFR-expressing cancerous tissues with nucleic acid drugs.

Uptake of epidermal growth factor (EGF)- and GE11-positive
exosomes by breast cancer cell lines

exosomes

(a) Flow cytometric analysis of epidermal growth factor receptor (EGFR) expression on HCC70, HCC1954, and MCF-7 breast cancer cells. (b) Uptake of fluorescently labeled exosomes by the breast cancer cell lines was detected using flow cytometry. PKH67-labeled exosomes were incubated with the breast cancer cell lines at 37 °C or 4 °C for 4 hours. The degree of uptake was relatively low at 4 °C. (c) Intracellular PKH67-labeled exosomes were detected in HCC70 cells (arrows) using confocal fluorescence microscopy. (d) Flow cytometric analysis of EGFR expression on MCF-7 cells, which were stably infected with retrovirus expressing EGFR. (e) Uptake of PKH67-labeled EGF- and GE11-positive exosomes was compared using MCF-7 cells expressing high levels of EGFR and control cells. (f) Uptake of PKH67-labeled EGF- and GE11-positive exosomes was compared among EGFRLow HCC70, EGFRHigh, and control cells.

Ohno SI, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M. (2017) Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells. Mol Ther 21(1):185-191. [article]

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