Consuming intracellular glucose and regulating the levels of O/HO via the closed cascade catalysis system of Cu-CeO nanozyme and glucose oxidase.

Imbalances in the intracellular environment caused by high levels of glucose, HO, 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, HO and O. The system, named DMSN@Cu-CeO@GOx, consists of Cu-CeO 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 HO. Cu-CeO then catalyzes the conversion of HO to O 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 O in cells. This hybrid nanomaterial offers a means to regulate the glucose/HO/O levels in cells and may provide insights into starvation therapy by modulating reactive species within cells.