4.7 Article

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

Journal

MOLECULAR THERAPY
Volume 21, Issue 1, Pages 185-191

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2012.180

Keywords

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Funding

  1. Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
  2. MEXT (Japan)
  3. Tokyo Medical University Cancer Research Foundation (Japan)
  4. Grants-in-Aid for Scientific Research [23590417, 23659626, 23659192] Funding Source: KAKEN

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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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