Hollow COF Capsules Co-Immobilizing Enzymes and Nanozymes: A Biomimetic Cascade Nanoreactor for Versatile Biosensing

Cascade reactions integrating biocatalysis and chemical catalysis have gained extensive attention but are limited by enzyme instability, poor carrier-enzyme compatibility, and mass transfer barriers. Herein, we report a novel polymer-assisted heterogeneous epitaxial growth strategy to fabricate hollow covalent organic framework (COF) capsules (HNKCOF-98), using ZIF-8 as a sacrificial template. Dual modification of ZIF-8 with polyvinylpyrrolidone (PVP) and branched polyethylenimine (BPEI) is critical, where BPEI provides amino sites for COF heterogeneous nucleation while PVP enhances dispersion and suppresses disordered fibrous growth by regulating monomer orientation. After removing the ZIF-8 core, HNKCOF-98 capsules with high crystallinity and specific surface area (1623 m 2 /g) are obtained. These capsules efficiently immobilize enzymes, maintaining their conformational flexibility and activity. The GOX&HRP@HNKCOF-98 cascade system exhibits excellent performance in glucose detection, with high stability and selectivity. Additionally, the XOD@HNKCOF-98@Pt biomimetic reactor achieves sensitive xanthine detection. This work expands COF morphological diversity and provides a versatile platform for high-performance enzyme immobilization and biosensing.