AbstractEnhancing or restoring enzymatic function in cells is highly desirable in applications ranging from ex vivo cellular manipulations to enzyme replacement therapies in humans. However, because enzymes degrade in biological milieus, achieving long-term enzymatic activities can be challenging. Herein we report on the in cellulo properties of nanofactories that consist of antioxidative enzymes encapsulated in metal–organic frameworks (MOFs). We demonstrate that, while free enzymes display weak activities for only a short duration, these efficient nanofactories protect human cells from toxic reactive oxygen species for up to a week. Remarkably, these results are obtained in spite of the nanofactories being localized in lysosomes, acidic organelles that contain a variety of proteases. The long-term persistence of the nanofactories is attributed to the chemical stability of MOF in low pH environment and to the protease resistance provided by the protective cage formed by the MOF around the encapsulated enzymes.