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
(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.