Remote-controlled multi-enzyme system for enhanced tumor therapy via dark/light relay catalysis

Abstract

Nanozymes have been widely used in biomedicine, especially in tumor therapy. However, inadequate H₂O₂ supply in the tumor microenvironment (TME) and uncontrolled catalytic activity of nanozymes in vivo restrict their practical application. Here, a dark/light relay strategy is proposed to realize adequate H₂O₂ supply in the dark reaction stage and selectively perform desired catalytic activities for toxic reactive oxygen species (ROS) generation to kill tumors by remote light control. A tumor membrane camouflaged and glucose oxidase (GOx) loaded hollow mesoporous Prussian blue (mGPB) nanosystem is designed to target tumor tissues for homologous aggregation of membranes. The cascaded catalysis of superoxide dismutase (SOD) and catalase (CAT)-like activities inherited from hollow mesoporous Prussian blue (HMPB) efficiently catalyze endogenous O₂⁻˙ to O₂, which contributes to the oxidative decomposition of glucose to produce H₂O₂ by loaded GOx. Moreover, mGPB nanoparticles are found to utilize H₂O₂ to produce ˙OH and ¹O₂ under NIR irradiation via other light-dependent dual-catalytic properties, acting as peroxidase (POD) and oxidase (OXD). By dark/light relay catalysis, we successfully overcome the limited H₂O₂ supply in TME and achieve precise ROS generation, displaying prominent tumor suppression in mouse xenograft models.