![Author ORCID: We display the ORCID iD icon alongside authors names on our website to acknowledge that the ORCiD has been authenticated when entered by the user. To view the users ORCiD record click the icon. [opens in a new tab]](https://chemrxiv.org/engage/assets/public/chemrxiv/images/logos/orcid.png)
Abstract
Metal-organic framework (MOF) biocomposites consist of MOF matrices into which biomacromolecules (e.g. proteins/enzymes) are immobilized for applications in drug delivery and biocatalysis. Zeolitic Imidazolate Frameworks (ZIFs) based on Zn2+ and 2-methylimidazole are the most studied MOFs for protein encapsulation. We systematically investigate how varying the Zn2+:2-methylimidazole:protein ratio, total precursor concentration, and washing procedure yields distinct Zeolitic Imidazolate Framework (ZIF) phases (ZIF-C, sod, dia) and amorphous forms. We find that each phase strongly influences crucial properties, including encapsulation efficiency (EE%), loading capacity (LC%), and release kinetics. Notably, we achieve unprecedented LC values (up to ~85%), ensuring a minimal carrier fraction while enabling high protein content. Using bovine serum albumin (BSA) as a model protein, we establish the relationships between precursors, crystallographic phase, EE%, LC%, and release profiles. We further encapsulate α-1-antitrypsin (AAT), a protein-based biotherapeutic, in ZIF-C, sod, and dia, verifying retained inhibitor activity upon release. Moreover, we demonstrate that blending rapid-releasing phases (sod) with slower ones (dia) enables multi-step release profiles, which are highly desirable for controlled drug delivery. These results highlight the pivotal role of systematic phase control to tune protein loading and release, offering a solid foundation for the rational design of ZIF-based biocomposites in advanced biomedical applications.
