Engineered E. coli for Long-Term Oral Enzyme Delivery

Intestinal flora shows excellent affinity in the gut, and the adhesive property is borrowed for oral drug delivery. A facile strategy for bacteria engineering has been successfully developed by introducing metal-organic framework (MOF) mineralization. The MOF exoskeleton serves as an extendable platform for accommodating various cargoes with good Escherichia coli morphology maintained. The artificial exoskeleton surrounding E. coli is employed for encapsulating macromolecules as a therapeutic cargo, maintaining good bioactivity with high immobilization efficiency (60%) after systematic optimization of the MOF precursor. Leveraging the natural affinity of E. coli in the gut, the in-vivo tracking of MOF-engineered E. coli in the gastrointestinal tract confirmed excellent adhesion to the GI mucosa and a 17.9-fold increase in the gut retention half-time, demonstrating significant advantages in retention capability. In comparison, the control group without E. coli equipment resulted in quick gut passage. Furthermore, the artificially engineered E. coli serves as an effective carrier for macromolecules without notable oral toxicity, as evidenced by biocompatibility evaluations in cells and animals. Overall, the MOF-engineered E. coli provides an extendable platform for loading on-demand cargoes in versatile therapeutic functions with promising clinical transnationality for long-term applications.