Abstract

An array of new nanomaterials have been designed to mimic the catalyst characteristics of natural enzymes (termed "nanozymes"), which connects an essential bridge between nanotechnology and biomedical science. Thus, the research on nanozymes has increased dramatically and a new multidisciplinary field has emerged in recent years named nanozymology. Magnetic iron oxide nanoparticles (e.g., Fe2O3 and Fe3O4, MIONs) have revealed to perform an enzyme-like activity with pH-dependent behavior. These nanozymes can catalytically decompose H2O2 into products (e.g., H2O and O2) under mild pH conditions mimicking enzyme-like bioactivity. More importantly, under mildly acidic conditions, they can use H2O2 as the substrate for producing highly toxic reactive oxygen species (ROS) through the generation of hydroxyl radicals (OH), displaying peroxidase-like activity. Therefore, here we designed and developed a novel class of hybrid nanocatalysts based on the conjugation of GOx (natural enzyme) and MIONs (inorganic nanozyme) stabilized by a biocompatible polymer shell of carboxymethyl cellulose. They created supramolecular vesicle-like nanostructures that were tested for killing brain cancer cells (U-87 MG) in vitro, where they proved anticancer activity attributed to ferroptosis-induced cell death. These hybrid nanostructures performed as a cascade of integrated nanocatalysts: a) GOx worked as the starting catalyst, where the glucose in the medium generated H2O2; b) next, H2O2 was catalyzed by the downstream MION nanozymes (Fe3O4) via Fenton-like reactions releasing toxic species (ROS), which caused the cancer cell death. Remarkably, this nanozyme-induced cell death was more pronounced in brain cancer cells ascribed to the more acidic microenvironment than on healthy cells.

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