title: Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Ohno
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Takanashi
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ueda
authors.forename: Akio
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Matsuyama
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mizutani
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Ohgi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.forename: Noriko
authors.initials: N
authors.lastname: Gotoh
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D066246:ErbB Receptors / Q000235:genetics*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage*; D016253:Microscopy, Immunoelectron; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; D066246:ErbB Receptors