Abstract: | Synthetic polymer vesicles spur novel strategies for producing intelligent nanodevices with precise and specific functions. Engineering vesicular nanodevices with tunable permeability by a general platform without involving trade‐offs between structural integrity, flexibility, and functionality remains challenging. Herein, we present a general strategy to construct responsive nanoreactors based on polyion complex vesicles by integrating stimuli‐responsive linkers into a crosslinking membrane network. The formulated ROS‐responsive nanoreactor with self‐boosting catalytic glucose oxidation could protect glucose oxidase (GOD) to achieve cytocidal function by oxidative stress induction and glucose starvation, which is ascribed to stimuli‐responsive vesicle expansion without fracture and size‐selective cargo release behavior. The GOD‐loaded therapeutic nanoreactor induced an immunostimulatory form of cell death by pyroptosis, which has the great potential to prime anti‐tumor immune responses. |