Spatiotemporal Proximity‐Enhanced Biocatalytic Cascades Within Metal–Organic Frameworks for Wearable and Theranostic Applications

Enzymatic catalysis, particularly multi‐enzyme cascade catalytic, is often limited by the spatial and temporal separation of enzymes and their signal substrates. Herein, a facile method for producing a spatiotemporal proximity‐enhanced biocatalytic cascade system is introduced by encasing enzymes within metal–organic frameworks (MOFs) that are modulated with sulfonic acid‐functionalized signal substrates. The modulated behavior relies on the sulfonic acid groups coordinated with Zn2+. As a proof of concept, by utilizing 2,2′‐Azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid ammonium salt) (ABTS), a widely‐used signal substrate for horseradish peroxidase, two‐enzyme/substrate, and three‐enzyme/substrate MOFs, which demonstrated a 7.4‐ and 10.2‐fold increase in biocatalytic efficiency over free systems are successfully synthesized. Incorporating the synthesized MOFs into homemade wearable patches and in vivo settings, noninvasive sweat glucose colorimetric detection and photoacoustic imaging‐guided photothermal tumor therapy are enabled, respectively. This advancement stems from the newly established coordinative bonds between Zn2+ centers and substrates' sulfonic acid groups, which negates the need for additional signal substrates, thereby not only enhancing but also streamlining bioapplication processes.