ZIF-8 functionalized alginate-chitosan hybrid microspheres as a versatile platform for α-glucosidase immobilization...

Efficient immobilization of α-glucosidase (α-Glu) is crucial for its application in inhibitor screening, but conventional polysaccharide hydrogels suffer from limited mechanical strength and stability. We hypothesized that a hybrid hydrogel synergistically integrating covalent polymer cross-linking with metal-organic framework (MOF) nanoparticles would overcome these limitations.

ZIF-8 reinforced alginate-chitosan (SC/ZIF-8) microspheres were fabricated via NHS/EDC-mediated covalent cross-linking and Ca²⁺-induced gelation. ZIF-8 incorporation dramatically enhanced mechanical strength (complex modulus increased >5-fold) and modulated swelling. The immobilized α-Glu@SC/ZIF-8 preserved intrinsic enzyme activity, exhibited superior pH stability (retaining ∼90% activity at pH 9.0), and demonstrated exceptional reusability (nearly 100% activity after 13 cycles) and storage stability (>95% after 28 days). Coupled with HPLC-MS/MS, the platform successfully identified batatasin I and 2,4-dimethoxy-6,7-dihydroxyphenanthrene as α-glucosidase inhibitors from Dioscorea opposita Thunb. Peel extracts.

This work presents a robust, biocompatible, and reusable biocatalytic platform that addresses key limitations of existing immobilization systems. The SC/ZIF-8 hybrid strategy offers a versatile foundation for enzyme-based screening in natural product drug discovery.