A chemodynamic nanoenzyme with highly efficient Fenton reaction for cancer therapy

Chemodynamic therapy (CDT) is a rising technology for cancer therapy by converting intracellular hydrogen peroxide (H2O2) into hydroxyl radical (center dot 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 for in vitro and in vivo antitumor therapy. A new MnFe2O4 nanoparticle 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 H2O2 and glutathione (GSH) in tumor tissue provided a favorable microenvironment for in situ generation of toxic free radicals. Fe3+ and GSH triggered a redox reaction to produce Fe2+, which in turn catalyzed H2O2 into center dot 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 both in vitro and in 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.