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.　©　2024　The　Author(s)