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

TLDR

Nucleic acid drugs hold therapeutic promise but are hampered by inadequate delivery systems, while exosomes—small endosomal vesicles secreted by diverse cells—offer a natural delivery platform. Targeting was achieved by engineering donor cells to express a platelet‑derived growth factor receptor transmembrane domain fused to the GE11 peptide, enabling exosomes to bind EGFR. Exosomes efficiently delivered let‑7a miRNA to EGFR‑expressing breast cancer cells and xenograft tumors in mice, demonstrating that engineered exosomes can therapeutically target EGFR‑positive cancers with nucleic acid drugs.

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.