Cu-MOF chemodynamic nanoplatform via modulating glutathione and H2O2 in tumor microenvironment for amplified cancer therapy

Abstract

Chemodynamic therapy (CDT) utilizes Fenton catalysts to convert intracellular hydrogen peroxide (H₂O₂) into cytotoxic hydroxyl radical (OH∙) for tumor therapy, but endogenous H₂O₂ is usually insufficient to achieve satisfactory tumor therapy effect. Engineering an efficient CDT nanoplatform for satisfactory cancer therapy remains a challenge. Herein, we rationally designed a Cu-based metal-organic framework-199 (MOF-199) nanoplatform integrating vitamin k3 (Vk3) for amplified CDT-mediated cancer therapy, which could accumulate efficiently in tumor tissues through enhanced permeability and retention (EPR) effect. The MOF-199 nanoparticles (MOF-199 NPs) were dissociated by glutathione (GSH) into MOF-199 fragments, which triggered Fenton-like reaction for CDT. On the one hand, Vk3 was catalyzed by NAD(P)H quinone oxidoreductase-1 (NQO1) to produce sufficient H₂O₂ to activate Fenton-like reaction. On the other hand, GSH was largely consumed in the tumor microenvironment. Thus, this nanoplatform enabled sufficient cytotoxic reactive oxygen species (ROS) for amplified CDT effect, demonstrating effective tumor growth inhibition with minimal side-effect in vivo. Our work provides an innovative strategy to modulate GSH and H₂O₂ levels for amplified CDT.

Keywords: Chemodynamic therapy; Cu-MOF; GSH; H(2)O(2); Nanoplatform.