Biomimetic Hybrid Nanozymes with Self-Supplied H⁺ and Accelerated O₂ Generation for Enhanced Starvation and Photodynamic Therapy against Hypoxic Tumors

Nanozymes as artificial enzymes that mimicked natural enzyme-like activities have received great attention in cancer diagnosis and therapy. Biomimetic nanozymes require more consideration regarding complicated tumor microenvironments to mimic biological enzymes, thus achieving superior nanozyme activity in vivo. Here we report a biomimetic hybrid nanozyme (named rMGB) which integrates natural enzyme glucose oxidase (GOx) with nanozyme manganese dioxide (MnO₂) by mutual promotion for maximizing the enzymatic activity of MnO₂ and GOx. Under hypoxia environment, we observed that MnO₂ could react with endogenous H₂O₂ to produce O₂ for enhancing the catalytic efficiency of GOx for starvation therapy. Meanwhile, we confirmed that glucose oxidation generated gluconic acid and further improved the catalytic efficiency of MnO₂ subsequently. The biochemical reaction cycle, consisting of MnO₂, O₂, GOx, and H⁺, was triggered by the tumor microenvironment and accelerated each other so as to achieve self-supplied H⁺ and accelerate O₂ generation, enhancing the starvation therapy, alleviating tumor hypoxia and accelerating the reactive oxygen species generation in photodynamic therapy. This biomimetic hybrid nanozyme would further facilitate the development of biological nanozymes for cancer treatment.