Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer

Abstract

Engineered exosomes have become popular drug delivery carriers for cancer treatment. This is partially due to the interesting property, i.e. exosome organotropism, which plays important role on organ distribution post systemic administration. Here, we demonstrated that breast cancer (MDA-MB-231) cell-derived exosomes (231-Exo) could be specifically internalized by non-small cell lung cancer cells via specific interaction between overexpressed integrin β4 (on exosomes) and surfactant protein C (SPC) on the cancer cells. We showed that 231-Exo was capable of recognizing A549 cells in blood and effectively escaping from immune surveillance system in vitro. Once loaded with microRNA molecule in the exosome carriers, the resulting, miRNA-126 loaded 231-Exo (miRNA-231-Exo) strongly suppressed A549 lung cancer cell proliferation and migration through the interruption of PTEN/PI3K/AKT signaling pathway. Intravenous administration of the miRNA-126 laden exosomes led to an effective lung homing effect in mice. When tested in a lung metastasis model, miRNA-231-Exo resulted in efficacious effect in inhibiting the formulation of lung metastasis in mice. Collectively, our data demonstrated the possibility for using organotropism feature of exosomes in nanocarrier design, generating potent anti-metastasis effect in a mouse model.