Adenosine Triphosphate‐Activated Cascade Reactor for On‐Demand Antibacterial Treatment Through Controlled Hydroxyl Radical Generation

Abstract Nanozymes have shown promise for antibacterial applications, but their effectiveness is often hindered by low catalytic performances in physiological conditions and uncontrolled production of hydroxyl radicals (·OH). To address these limitations, a comprehensive approach is presented through the development of an adenosine triphosphate (ATP)‐activated cascade reactor (GGPcs). The GGPcs reactor synergistically combines the distinct properties of zeolitic imidazolate framework‐8 (ZIF‐8) and chitosan‐integrated hydrogel microsphere. The ZIF‐8 allows for the encapsulation of G‐quadruplex/hemin DNAzyme to achieve ATP‐responsive ·OH generation at neutral pH, while the hydrogel microsphere creates a confinement environment that facilitates glucose oxidation and provides a sufficient supply of H 2 O 2 . Importantly, the integrated chitosan in the hydrogel microsphere shields ZIF‐8 from undesired disruption caused by gluconic acid, ensuring the responsive specificity of ZIF‐8 toward ATP. By activating GGPcs with ATP secreted by bacteria, its effectiveness as an antibacterial agent is demonstrated for the on‐demand treatment of bacterial infection with minimal side effects. This comprehensive approach has the potential to facilitate the design of advanced nanozyme systems and broaden their biological applications.