A Dual-Metabolic Strategy Combining pH-Responsive Vascular Embolization and Localized Glucose Oxidase Delivery for...

Conventional tumor starvation via embolization or glucose oxidase (GOx) is often hampered by poor specificity and enzyme instability. Herein, we developed a pH-responsive, amphiphilic GOx-conjugated polymer (LPHF-GOx) for synergistic cascade starvation therapy. Triggered by the acidic tumor microenvironment, LPHF-GOx undergoes rapid aggregation, achieving dual metabolic disruption through localized vascular embolization and GOx-mediated glucose depletion. LPHF-GOx demonstrated robust pH-dependent self-assembly while maintaining high catalytic activity. In vitro and in vivo evaluations confirmed that this dual-action system induces profound nutrient deprivation and oxidative stress, leading to significant tumor growth inhibition with negligible systemic toxicity. By integrating vessel occlusion with biochemical enzymatic interference, this study provides a potent and targeted platform for sustainable starvation therapy against malignant tumors.