Rapid Fabrication of Biocomposites by Encapsulating Enzymes into Zn-MOF-74 via a Mild Water-Based Approach

Abstract

A zinc-based metal organic framework, Zn-MOF-74, which has a unique one-dimensional (1D) channel and nanoscale aperture size, was rapidly obtained in 10 min using a de novo mild water-based system at room temperature, which is an example of green and sustainable chemistry. First, catalase (CAT) enzyme was encapsulated into Zn-MOF-74 (denoted as CAT@Zn-MOF-74), and comparative assays of biocatalysis, size-selective protection, and framework-confined effects were investigated. Electron microscopy and powder X-ray diffraction were used for characterization, while electrophoresis and confocal microscopy confirmed the immobilization of CAT molecules inside the single hexagonal MOF crystals at loading of ∼15 wt %. Furthermore, the CAT@Zn-MOF-74 hybrid was exposed to a denaturing reagent (urea) and proteolytic conditions (proteinase K) to evaluate its efficacy. The encapsulated CAT maintained its catalytic activity in the decomposition of hydrogen peroxide (H 2 O 2 ), even when exposed to 0.05 M urea and proteinase K, yielding an apparent observed rate constant (k obs ) of 6.0 × 10 −2 and 6.6 × 10 −2 s −1 , respectively. In contrast, free CAT exhibited sharply decreased activity under these conditions. Additionally, the bioactivity of CAT@Zn-MOF-74 for H 2 O 2 decomposition was over three times better than that of the biocomposites based on zeolitic imidazolate framework 90 (ZIF-90) owing to the nanometer-scaled apertures, 1D channel, and less confinement effects in Zn-MOF-74 crystallites. To demonstrate the general applicability of this strategy, another enzyme, α-chymotrypsin (CHT), was also encapsulated in Zn-MOF-74 (denoted as CHT@Zn-MOF-74) for action against a substrate larger than H 2 O 2 . In particular, CHT@Zn-MOF-74 demonstrated a biological function in the hydrolysis of Lphenylalanine p-nitroanilide (HPNA), the activity of ZIF-90-encapsulated CHT was undetectable due to aperture size limitations. Thus, we not only present a rapid eco-friendly approach for Zn-MOF-74 synthesis but also demonstrate the broader feasibility of enzyme encapsulation in MOFs, which may help to meet the increasing demand for their industrial applications.

Metal Azolate Coordination Polymer-Enabled High Payload and Non-Destructive Enzyme Immobilization for Biocatalysis and Biosensing

“…As listed in Table 1, ZnCP exhibited ultrahigh protein loading contents, which exceeded most of the reported MOF shown in Table S1 in the Supporting Information. 13,14,30 Encouraged by the good encapsulation performance of ZnCP, we coimmobilized dual enzymes (Cyt c and GOx) within ZnCP to construct an enzyme cascade reactor (Cyt c-GOx@ZnCP) for glucose biosensing. In this system, glucose was first catalyzed by the embedded GOx to yield H 2 O 2 , which subsequently oxidized ABTS to form green ABTS• + in the presence of adjacent Cyt c, enabling specific colorimetric assay of glucose (Figure 5a).…”

Microfluidic Synthesis of a Bioactive Metal–Organic Framework for Glucose-Responsive Insulin Delivery

“…1 Here, metal−organic frameworks (MOFs) have emerged as favorable systems due to their intrinsic properties such as high surface areas, large pore volumes, tunable pore sizes, high crystallinity, and customizable organic ligands. 2 Hence, they have been explored in numerous technological areas, including chemical separation, 3 gas sensing, 4 electromagnetic wave absorption, 5 enzyme encapsulation, 6 environmental pollution control, 7 and the healthcare applications being in biosensing, 8 storage 9 and delivery 10 of nitric oxide, and scaffolds 6 for compatible bone reinforcement or wound healing, 11,12 as delivery agents for imaging, chemotherapy, photothermal therapy, and intracellular delivery of proteins, nucleic acids, and aptamers. 13 Zeolitic imidazolate framework-8 (ZIF-8) is a novel class of MOFs that is formed by the self-assembly between Zn 2+ and imidazolate using a simple, one-pot approach.…”

Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod

“…Metal–organic framework (MOF), a porous coordination polymer consisting of metal nodes and organic linkers, receives wide interests in biomedical applications to imaging, biocatalysis, and drug delivery due to its high surface area, modulated porosities, flexible/versatile chemical composition/reactivity, and biodegradability under certain conditions. − To utilize MOF as an oral drug delivery system (or an orally active drug), , high-valence metal center (Fe 3+ , Y 3+ , Zr 4+ , Ti 4+ ) and exquisite design of organic linker (benzenecarboxylic acids and their derivatives) are critical to improve its stability under acidic environment, − to enhance its biocompatibility, , and to facilitate the loading of drug/cargo through noncovalent interactions (Table S1). − For example, confinement of insulin (or aspirin) in acid-resistant NU-1000 (or MIL-100­(Fe)) facilitates the exceptional stability of Insulin@NU-1000 (or ASA@MIL-100­(Fe)) under simulated gastric condition (pH 1.2), whereas phosphate-triggered degradation of NU-1000 under simulated physiological condition (pH 7.0) triggers the release of encapsulated insulin. , On the other hand, incorporation of a nitrogen heterocycle in the aromatic di-/tricarboxylate linkers into Zr 4+ -/Y 3+ -based MOFs enables the pH-responsive loading/release of drugs (i.e., ibuprofen, diclofenac) through the formation/cleavage of hydrogen-bonding interaction with the protonated/nonprotonated linker under acidic/neutral environment. − In addition to acid-resistant MOFs, encapsulation of Drug@MOF conjugates in pH-responsive polymers (i.e., carboxymethylcellulose, gelatin, chitosan, mPEG- b -PLLA, montmorillonite) was also reported to enhance gastrointestinal drug delivery and therapeutic efficacy (Table S1).…”