Engineered Hybrid Nanosystem for Homologous Targeting of EMT Induced Triple Negative Breast Cancer Cells.

Abstract

The increased mortality rate due to metastatic breast cancer with poor prognosis has raised concern over its effective therapy. Though various therapies and anticancer drugs have been approved, there is still a lack in the targeting of metastatic triple negative breast cancer (TNBC). We have developed a hybrid nanosystem that was synthesized by fusing exosomes from MCF-7 cells and nanovesicles from the MDA MB-231 cells that would be targeted. The developed nanosystem was characterized by various techniques like Western blotting, AFM, FETEM, DLS, CD, and fluorescence spectroscopy. The hybrid system was used for the delivery of an HDAC inhibitor, Trichostatin A (TSA), in combination with lapatinib (a tyrosine kinase inhibitor) for cotherapy of epithelial to mesenchymal transition (EMT) induced TNBC. This targeted cotherapy module had higher efficiency and effectivity in the reduction of metastatic ability and proliferation of EMT induced MDA MB-231 cells as compared to free inhibitor treatment or untargeted cotherapy. Reduction in the expression of the Wnt/β-catenin signaling pathway molecules like β-catenin (by 0.7 fold), Gsk3β (by 0.6 fold), and pGsk-3β (0.3 fold) was observed upon treatment. This subsequently resulted in the suppression of EMT markers, thereby resulting in reversing EMT to MET and suppressing metastatic breast cancer.