Nanoarchitectonics of Metal–Organic Framework Platforms for Enhanced Enzyme Delivery with Preserved Activity

The targeted delivery of biomacromolecules remains a critical challenge due to their intrinsic instability, limited permeability across biological barriers, and susceptibility to degradation. Herein, we report postsynthetic enzyme encapsulation in reaction-mechanism-guided metal-organic framework nanocarriers (MOF NCs), enabling selective loading, controlled release, and preserved biological function. The MOF NCs were synthesized via coordination-driven assembly, yielding hybridized porous architectures with high colloidal stability in aqueous media. Enzyme encapsulation was accomplished through nondisruptive interactions, including hydrogen bonding, ionic interactions, covalent anchoring, or van der Waals interactions. The structural integrity of β-Dextranase and endo-1,4-β-mannanase, enzymes known to disrupt oral biofilms, was maintained throughout encapsulation and release, as confirmed by circular dichroism spectroscopy. Environmentally responsive enzyme release was triggered under mildly acidic or alkaline conditions, driven by ligand exchange and hydrolysis at the zinc coordination centers, leading to nanocarrier disassembly and subsequent enzymatic activation. The MOF NCs exhibited excellent biocompatibility and preserved enzyme activity comparable to free enzymes at acidic and basic pH values, demonstrating their potential for targeted therapeutic applications at otherwise inaccessible biological sites.