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

被引:1468
作者
Ohno, Shin-ichiro
Takanashi, Masakatsu
Sudo, Katsuko [2 ]
Ueda, Shinobu
Ishikawa, Akio
Matsuyama, Nagahisa
Fujita, Koji
Mizutani, Takayuki
Ohgi, Tadaaki [3 ]
Ochiya, Takahiro [4 ]
Gotoh, Noriko [5 ]
Kuroda, Masahiko [1 ]
机构
[1] Tokyo Med Univ, Dept Mol Pathol, Shinjuku Ku, Tokyo 1608402, Japan
[2] Tokyo Med Univ, Anim Res Ctr, Tokyo 1608402, Japan
[3] BONAC Corp, Fukuoka BIO Factory 4F, Fukuoka, Japan
[4] Natl Canc Ctr, Res Inst, Div Mol & Cellular Med, Tokyo 104, Japan
[5] Univ Tokyo, Inst Med Sci, Div Syst Biomed Technol, Tokyo, Japan
关键词
GROWTH-FACTOR RECEPTOR; PEPTIDE LIGAND; LET-7; GENE; EXPRESSION; REPRESSES;
D O I
10.1038/mt.2012.180
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:185 / 191
页数:7
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