Raising enzymatic stability during biocatalysis with hierarchically hollow two-dimensional MOF nanocapsules

Metal-organic frameworks (MOFs) have emerged as promising platforms for enzyme immobilization. Nevertheless, conventional MOF carriers encounter challenges, including restricted catalytic activity and inadequate acid stability, thereby limiting their applicability in oncological contexts. Here, glucose oxidase and ZIF-8 (a common MOF carrier) are chosen as models. Hierarchically hollow two-dimensional conjugated MOF (Zn-HHTP [zinc 2,3,6,7,10,11-hexahydroxytriphenylene]) nanocapsules are constructed by a mild ZIF-8-to-Zn-HHTP transformation at room temperature to boost the ex vivo and in vivo biocatalytic activity and stability of enzymes. The hierarchical Zn-HHTP nanocapsules feature hollow nanostructures and mesoporous-microporous structures (4.2 and 1.2 nm), which are beneficial for enhanced biocatalytic activity and maintaining enzyme conformation. Glucose oxidase@Zn-HHTP exhibits 2.5 times higher catalytic activity than that of glucose oxidase@ZIF-8. Importantly, nanocapsules exhibit higher acid stability than the parental ZIF-8, allowing them to stably traverse the acidic microenvironment of a tumor and achieve intracellular glucose detection to discriminate normal and cancerous cells.