Metal‐Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Abstract

Protein therapeutics are prone to lose their structure and bioactivity under various environmental stressors. Herein, we report a facile approach using a nanoporous material, zeolitic imidazolate framework-8 (ZIF-8), as an encapsulant for preserving the prototypic protein therapeutic, insulin, against different harsh conditions that may be encountered during storage, formulation and transport, including elevated temperatures, mechanical agitation and organic solvent. Both immunoassay and spectroscopy analysis demonstrate the preserved chemical stability and structural integrity of insulin offered by the ZIF-8 encapsulation. Biological activity of ZIF-8 preserved insulin after storage under accelerated degradation conditions (i.e. 40°C) was evaluated in vivo using a diabetic mouse model, and showed comparable bioactivity to refrigeration-stored insulin (−20°C). We also demonstrate that ZIF-8 preserved insulin had low cytotoxicity in vitro and did not cause side effects in vivo. Furthermore, ZIF-8 residue can be completely removed by a simple purification step before insulin administration. This biopreservation approach is potentially applicable to diverse protein therapeutics, thus extending the benefits of advanced biologics to resource-limited settings and underserved populations/regions.

Degradation of ZIF-8 in phosphate buffered saline media

“…[11][12][13][14][15] Zeolitic imidazolate framework-8 (ZIF-8), composed of tetrahedral Zn 2+ ions linked by 2-methylimidazolate (mIM) ligands, is one of the most studied MOF carriers. [16][17][18][19][20] The widespread interest in ZIF-8 can be attributed the following reasons: 1) encapsulation of APIs and biomolecules within ZIF-8 can be carried out in aqueous media, 16,20 2) the loading and release efficiency can reach 100%, 20 3) the protection of biomolecules in ZIF-8 can be extended to conditions that would typically result in their degradation (e.g. high temperature), 21 and 4) the release of APIs and biomolecules can be controlled either by lowering the pH below 6.5 or adding chelating agents (e.g.…”

Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection

“…Notably, the thermally stressed CFT@ZIF formulation promoted longer survival, which hints at a possible thermally protective effect of the ZIF-8 shell, an observation that is with considerable precedence. [61][62][63]…”

Nanomaterials-Based Colorimetric Immunoassays

“…The unique composition, structural diversity, and tunable size make MOFs good alternatives for novel nanozymes [84]. Besides, MOFs can be a better candidate as a host for biomolecule encapsulation, because they can protect the biomolecules from harsh environments and preserve their original biological functions [85,86,87]. For the convenience of this review, we integrated covalent organic frameworks (COFs) and amorphous three-dimensional covalent organic polymer (COP) into this section.…”

“…Apart from the simple loading properties, nanomaterials can also preserve and enhance the catalytic activity of the encapsulated enzymes against different harsh conditions. For example, MOFs can also preserve and enhance the catalytic activity of the encapsulated enzymes due to the small pore size of MOFs and the coordination interaction between enzymes and MOFs [85,149]. GO can modulate the peroxidase-like property of lysozyme-stabilized Au NCs so that it shows high catalytic activity over a broad pH range, even at neutral pH [150].…”