Engineered exosome-based drug delivery system for synergistic cancer therapy via autophagy inhibition and chemotherapy

Abstract

Exosomes (EXOs) are a class of natural nanovesicles secreted endogenously by mammalian cells. Recent decades have witnessed the broad applications of exosomes in cancer diagnosis and treatment. In the present study, an exosome-based drug delivery system employing synergistic miRNA-based autophagy inhibition and 7-coumarin-based chemotherapy was established for ovarian cancer therapy. Taking advantage of the outstanding biocompatibility and immune evasion, exosomes are used as carriers for targeted drug delivery. Magnetic nanoparticles (MNPs) were coupled to exosomes to improve the separation efficiency of exosomes. Two drugs, miRNA-FAM and 7-coumarin, were loaded into EXOs-MNPs by electroporation to achieve the miRNA-FAM/7-coumarin@EXOs-MNPs drug delivery system. The engineered exosome-based drug delivery system improved the cell entry ability of drugs and the targeting of cancer cells. Simultaneous application of the two drugs significantly improved the efficacy of cancer cell therapy, indicating that the two drugs have synergistic effects. Therefore, this work provided a new drug delivery system and synergistic therapy idea, which showed great potential for future clinical applications.