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

Mol Ther. 2013 Jan;21(1):185-91. doi: 10.1038/mt.2012.180. Epub 2012 Oct 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Coculture Techniques
  • ErbB Receptors / genetics*
  • Exosomes / metabolism*
  • Female
  • Humans
  • Mice
  • MicroRNAs / administration & dosage*
  • Microscopy, Immunoelectron
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • ErbB Receptors