A chemodynamic nanoenzyme with highly efficient Fenton reaction for cancer therapy

Abstract

Chemodynamic therapy (CDT) is a rising technology for cancer therapy by converting intracellular hydrogen peroxide (H₂O₂) into hydroxyl radical (•OH) via transition-metal-containing nanoparticles (NPs) catalysis reaction (i.e. Fenton reaction) to kill tumor cells. Highly efficient Fenton reaction and favorable delivery of the catalytic NPs 'nanoenzyme' are the key for successful treatment of cancer. In this work, we developed a novel nanoenzyme MnFe₂O₄@GFP forin vitroandin vivoantitumor therapy. A new MnFe₂O₄nanoparticle containing two transition-metal-element Fe and Mn was synthesized for enhanced Fenton reaction and used to co-deliver protein with high biocompatibility through post-modification with dopamine polymerization, green fluorescent protein adsorption, and PEG coating. The enrichment of H₂O₂and glutathione (GSH) in tumor tissue provided a favorable microenvironment forin situgeneration of toxic free radicals. Fe³⁺and GSH triggered a redox reaction to produce Fe²⁺, which in turn catalyzed H₂O₂into •OH, with the consumption of antioxidant GSH. By combining Fe³⁺with another catalyzer, the catalytic efficiency of the nanoenzyme were greatly improved. Consequently, the nanoenzyme showed efficient antitumor ability bothin vitroandin vivo. Thus, the multifunctional CDT nanoenzyme platform shows great promising for antitumor therapy through the combination of catalyzers Fe³⁺and Mn²⁺and codelivery of protein cargo.

Keywords: MnFe2O4; chemodynamic therapy (CDT); hydroxyl radicals (•OH), tumor microenvironment (TME).