A Dual-Metabolic Strategy Combining pH-Responsive Vascular Embolization and Localized Glucose Oxidase Delivery for Cascade Starvation Therapy of Tumor

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.