Engineering Magnetic Extracellular Vesicles Mimetics for Enhanced Targeting Chemodynamic Therapy to Overcome Ovary Cancer.

Chemodynamic therapy (CDT), employing metal ions to transform endogenous HO into lethal hydroxyl radicals (OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and β-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective HO generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of HO into OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.