Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells

• Published in: Molecular therapy Vol. 21; no. 1; pp. 185 - 191
• Main Authors: Ohno, Shin-ichiro, Takanashi, Masakatsu, Sudo, Katsuko, Ueda, Shinobu, Ishikawa, Akio, Matsuyama, Nagahisa, Fujita, Koji, Mizutani, Takayuki, Ohgi, Tadaaki, Ochiya, Takahiro, Gotoh, Noriko, Kuroda, Masahiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2013; Elsevier Limited; Nature Publishing Group
• Subjects: Animals; Base Sequence; Blotting, Western; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - therapy; Cell Line, Tumor; Coculture Techniques; Exosomes - metabolism; Female; Humans; Mice; MicroRNAs - administration & dosage; Microscopy, Immunoelectron; Original; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1038/mt.2012.180

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, we 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. Our results suggest that exosomes can be used therapeutically to target EGFR-expressing cancerous tissues with nucleic acid drugs.