A Natural Enzyme GOx-MOF Cascade Complex Killing Zoonotic Parasite Trichinella spiralis by Energy Utilization Limitation and Generated Free Radicals.

Nanozymes offer promising alternatives to natural enzymes due to enhanced stability, tunable activity, and cost efficiency, demonstrating therapeutic potential against tumors, infections, and inflammatory disorders. Trichinella spiralis is an important pathogen, which globally prevalent foodborne zoonotic parasite. Chemical drug is commonly used to kill T. spiralis, but there are risks of chemical abuse and drug resistance. Here, we engineered MPG(Fe), a cascade nanozyme formed by covalently conjugating glucose oxidase (GOx) to a metal-organic framework-Fe nanozyme (MOF-525[Fe]) nanozyme via the bifunctional PEG linker. In vitro, MPG(Fe) depleted glucose through GOx-catalyzed conversion to gluconic acid and H2O2, while MOF-525(Fe) subsequently transformed H2O2 into cytotoxic hydroxyl radicals (•OH). This dual-action mechanism dose-dependently killed intestinal-stage adult worms and newborn larvae (NBL) of T. spiralis. In a BALB/c mouse model of intestinal T. spiralis infection, high-dose MPG(Fe) reduced the survival of intestinal adult worms to 3.53% of the control value through the synergistic actions of glucose deprivation and hydroxyl radical (•OH)-mediated oxidative damage. Critically, MPG(Fe) exhibited no tissue toxicity in uninfected mice. Our findings establish enzyme-mimetic nanozymes as a novel therapeutic platform against zoonotic helminthiases.