Crystallographic Continuity Enables Programmable Living Biointerfaces

Dynamic biological entities are versatile but remain vulnerable to immune clearance, premature chemical exchange, and environmental degradation. Metal–organic frameworks (MOFs) offer porous matrices for bioencapsulation; however, standard polycrystalline or nanoparticulate shells contain structural defects that compromise protective performance and molecular selectivity. Here, we demonstrate the complete encapsulation of viruses, bacteria, and mammalian erythrocytes within continuous single-crystalline ZIF-90 via biocompatible aqueous routes. Interfacial electrostatics and coordination kinetics shift the nucleation-growth balance to favor particle coalescence and crystallographic fusion at the biological surface. Unlike conventional nanoparticulate ZIF-8 coatings, continuous ZIF-90 single crystals restrict molecular access, shielding host bacteria from ultraviolet radiation and antibiotic stress while preventing premature immunostimulatory signaling. Under acidic conditions mimicking the tumor microenvironment, ZIF-90 degrades, releasing active Escherichia coli and exposing intracellular bacterial triggers. In vivo , these biohybrids induce pyroptotic cell death and suppress pulmonary metastasis. Crystallographic continuity thus provides a structural basis for coupling biological shielding with environment-responsive activation, establishing a physical foundation for programmable biointerfaces.