Статья

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

Shin‐ichiro OhnoDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanMasakatsu TakanashiDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanKatsuko SudoAnimal Research Center, Tokyo Medical University, Tokyo, JapanShinobu UedaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanAkio IshikawaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanNagahisa MatsuyamaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanKoji FujitaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanTakayuki MizutaniDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanTadaaki OhgiBONAC Corporation, Fukuoka BIO Factory 4F, Fukuoka, JapanTakahiro OchiyaNoriko GotohDivision of Systems Biomedical Technology, Institute of Medical Science, University of Tokyo, Tokyo, JapanMasahiko KurodaDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, Japan

2012en

ABI

Аннотация

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. 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.

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Идентификаторы

DOI: 10.1038/mt.2012.180

Цитирования и источники

Цитирований: 4Использованных источников: 0

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