Consuming intracellular glucose and regulating the levels of O2/H2O2 via the closed cascade catalysis system of Cu-CeO2 nanozyme and glucose oxidase

Abstract

Imbalances in the intracellular environment caused by high levels of glucose, H₂O₂, and hypoxia can greatly impact cancer development and treatment. However, there is limited research on regulating the levels of these species simultaneously in tumor cells. Here, a pH-responsive nanozyme-enzyme hybrid system was developed to regulate intracellular glucose, H₂O₂ and O₂. The system, named DMSN@Cu-CeO₂@GOx, consists of Cu-CeO₂ nanoparticles and glucose oxidase (GOx) immobilized in dendritic mesoporous silica (DMSN) spheres. GOx efficiently consumes glucose in tumor cells, causing a drop in pH and producing a significant amount of H₂O₂. Cu-CeO₂ then catalyzes the conversion of H₂O₂ to O₂ due to its high catalase-like (CAT) activity in weakly acidic conditions. The process was monitored by fluorescence probes, and the mechanism was investigated through fluorescence spectroscopy and confocal laser scanning microscopy. The cascade catalytic system with excellent biocompatibility continuously consumes glucose and elevates the level of O₂ in cells. This hybrid nanomaterial offers a means to regulate the glucose/H₂O₂/O₂ levels in cells and may provide insights into starvation therapy by modulating reactive species within cells.

Keywords: nanozyme-enzyme hybrid system; pH-responsive; reactive oxygen species; regulation; tandem catalysis.