Enzymatic Nanomotors Surviving Harsh Conditions Enabled by Metal Organic Frameworks Encapsulation

Abstract Enzyme‐driven micro/nanomotors (MNMs) have demonstrated potentials in the biomedical field because of their excellent biocompatibility, versatility, and fuel bioavailability. However, the fragility of enzymes limits their practical application, because of their susceptibility to denaturation and degradation in realistic scenarios. Herein, a simple yet versatile and effective approach is reported to preserve the enzymatic activity and propulsion capability of enzymatic MNMs under various harsh conditions using metal organic frameworks (MOFs) as a protective shell. Urease can be encapsulated within the exoskeleton of zeolitic imidazolate framework‐8 (ZIF‐8) via biomimetic mineralization to form ZIF‐8@urease (ZU‐I) nanomotors that exhibit self‐propulsion in the presence of urea. When exposed to harsh conditions, including high temperature, presence of proteases, and organic solvents, the ZU‐I nanomotors still maintained their activity and mobility, whereas ZIF‐8 with externally modified urease (ZU‐O) nanomotors with externally modified urease as a control rapidly lost their motion capabilities owing to the inactivation of urease. Furthermore, ZU‐I nanomotors exhibit effectively enhanced diffusion within the small intestine fluid, achieving a fourfold higher mucus penetration than the ZU‐O nanomotors. The results highlight the effectiveness of using MOFs as protective shells for enzyme nano‐engines, which can greatly advance the practical applications of enzymatic MNMs under realistic conditions, especially for biomedical purpose.