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

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H₂O₂ 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 H₂O₂ generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H₂O₂ 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.