Metal–Organic Framework-Integrated Enzymes as Bioreactor for Enhanced Therapy against Solid Tumor via a Cascade Catalytic Reaction

Emerging natural-enzyme-based nanocatalytic tumor therapy depending on the high catalytic performance of natural enzymes has inspired great research interest in clinical applications. Nevertheless, the natural-enzyme-based catalytic therapy efficiency is seriously hampered by the low operational stability, poor delivery efficiency, and the short lifetime of enzymes. Herein, a bioreactor based on zeolitic imidazolate framework-8 (ZIF-8) was fabricated through one-pot embedding horseradish peroxidase (HRP) and glucose oxidase (Gox) strategy (ZIF-8@Gox/HRP) for synergistic cancer therapy. Notably, the obtained ZIF-8@Gox/HRP can efficiently consume endogenous glucose to generate gluconic acid and H2O2 for starving tumors, and subsequently, H2O2 was decomposed by encapsulated HRP to release high-toxic •OH radicals, inducing cancer cell apoptosis for oxidation therapy. Importantly, in vivo results showed that ZIF-8@Gox/HRP had an impressive tumor-suppression rate based on cascade catalytic reaction. Therefore, this work paves a new avenue to design smart enzyme-based platforms for safe and efficient cancer therapy.