M1 Macrophage-Engineered Vesicles Have Anti-Cancer Activity in Ovarian Cancer.

Background: Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell membrane derived nanoparticles that function in specific cell-to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) from M1 macrophages are able to repolarize macrophages from a M2 to a M1 phenotype and target tumor cells in in vitro studies. Results: In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) with and without cisplatin to generate cisplatin-loaded MEVs (C-MEVs) and empty MEVs (E-MEVs), which we tested in an ovarian cancer mouse xenograft model. E-MEVs and C-MEVs exhibited significantly less weight loss and equivalent activity to cisplatin, with improved activity over controls. Conclusions: Further development of MEVs for the treatment of ovarian cancer is warranted.