Mater. Today 2026, 99, 103483

Abstract: Glucose oxidase (GOx)-based enzyme dynamic therapy (EDT) has emerged as a promising anticancer strategy, yet its therapeutic efficacy remains constrained by suboptimal enzyme conformation. Although framework materials have recently been developed to adjust enzyme conformation, GOx conformational optimization remains challenging due to complex subunits. Here, supramolecular chiral nanocarriers successfully immobilize GOx and realize overall conformational optimization of GOx via enhanced stereoselective binding, efficiently improving GOx catalytic activity as well as tumor therapeutic efficiency. Chirality-mediated binding affinity between L-type nanocarriers (LPH) and GOx drives a loose conformation in GOx, facilitating the exposure of enzymatic active sites from the hydrophobic pocket. This optimized configuration enhances active site accessibility, yielding 35% greater enzymatic activity than free GOx. Integration of horseradish peroxidase (HRP) with LPH@GOx nanocarrier (LPH@GH) remarkably promotes production of ·OH and oxidative therapeutic effect. With these cascade reactions, LPH@GH exhibits starvation-oxidative bimodal therapeutic effect, leading to in vivo tumor necrosis (1.6 fold tumor growth inhibition compared with free enzymes). This chiral nanocarrier not only efficiently improves the GOx-based anticancer therapy effects but also presents autofluorescence, allowing real-time tumor detection for integrated tumor diagnosis and therapy.

https://doi.org/10.1016/j.mattod.2026.103483