Glucose oxidase-powered nanocatalytic medicine: Rewiring tumor metabolism for multimodal cancer therapy

Cancer cells exhibit metabolic reprograming characterized by a preference for aerobic glycolysis (the Warburg effect), which supports their rapid proliferation while promoting immune invasion and microenvironment remodeling. Glucose oxidase (GOX) has emerged as a powerful therapeutic agent that exploits this metabolic vulnerability through targeted glucose depletion. Recent advances in nanocarrier technology have addressed critical limitations of native GOX, including systemic toxicity, short circulation half-life, immunogenicity, and instability in physiological environments. Engineered GOX nanoconstructs demonstrate remarkable tumor-specific cytotoxicity through dual mechanisms: (1) starvation via glucose deprivation and (2) oxidative damage through reactive oxygen species generation. Importantly, GOX-mediated modulation of tumor microenvironment parameters - acidity, H₂O₂ concentration, and oxygen tension - creates favorable conditions for combination therapies. This catalytic synergy enhances the efficacy of diverse treatment modalities including chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, gas therapy, and immunotherapy. This review comprehensively examines recent progress in GOX-based nanocatalytic platforms, focusing on their design principles, therapeutic mechanisms, and potential for multimodal cancer treatment.