Carbohydrates@MOFs

Abstract

MOFs have demonstrated outstanding properties for the protection and controlled release of different bio-entities, from proteins to living cells. Carbohydrates, as pure molecules or as a component of proteins and cells, perform essential biological functions. Thus, an understanding of the role of carbohydrates in the formation of MOF-based bio-composites will facilitate their application to biotechnology and medicine. Here, we investigate the role of carbohydrate molecular weight and chemical functionalization in the formation of carbohydrate@MOF composites. We find that chemical functionalization, such as carboxylation, that leads to an enhancement of metal cation concentration at the surface of the molecule triggers the rapid self-assembly of the MOF material, zeolitic-imidazolate framework 8 (ZIF-8). Furthermore, we determine the encapsulation efficiency and measure the release properties of the carbohydrate under controlled conditions. Our findings show that MOFs can be used to prepare a new class of biocomposites for the delivery of carbohydrate-based therapeutics. † Electronic supplementary information (ESI) available: Additional figures, movies and experimental details. Substrates used and their formulas, schematic overviews of the performed syntheses and workups, time-dependent MOFformation experiments induced by different carbohydrates and concentrations, yield calculations, SEM image of ZIF-8 on glass and paper, FTIR spectra of the starting materials and the obtained products, schematic of the ion-permeable spherical model, kinetics studies, UV-Vis analyses, photographs of solutions using different polysaccharides, and video showing the succesfull biomimetic mineralisation of CM-dextran. SeeCarbohydrate-based therapeutics are relevant drugs for the treatment of cancer, diabetes, viral and bacterial infections. Therefore the efficient encapsulation and controlled release of carbohydrates has great potential in biomedicine. Here, we present a successful strategy to trigger the spontaneous crystallization of metal-organic frameworks (MOFs) on carbohydrates. The encapsulation of carbohydrates within ZIF-8 and polymorphs (zinc-imidazolate-based MOFs) can be obtained in water. The identification of conditions suitable for the successful preparation of the composite were experimentally and computationally identified. By controlling the chemical functionalization of the carbohydrate, the formation of bio-composites can be obtained in seconds. A 100% encapsulation efficiency was obtained. The controlled release of carbohydrates from the MOF biocomposite was demonstrated. This proof-of-concept study shows that a new generation of MOF biocomposites can be exploited for biomedical applications.

Encapsulation, Visualization and Expression of Genes with Biomimetically Mineralized Zeolitic Imidazolate Framework‐8 (ZIF‐8)

“…To confirm that the DNA did not stay in the supernatant during plGFP@ZIF‐8 synthesis, both the supernatant and the EDTA‐treated pellets were run on a 1% agarose gel electrophoresis ( Figure A). ZIF‐8 particles can be dissolved by means of either EDTA or an acid buffer . A distinct band was visible in the pellet lane, which is similar in intensity to the pure DNA control.…”

“…Zeolitic imidazolate frameworks (ZIFs) are members of the MOF family and are made of zinc ions coordinated by imidazole rings to form topological isomorphs of zeolites . They have demonstrated biocompatibility, biodegradability, protection, and potential applications in antitumor therapy, protection of biomarkers, and encapsulation of therapeutics . Several nano MOFs, including ZIFs, have been used successfully to deliver small interfering ribonucleic acids (siRNAs) and oligonucleotides, and encapsulation of proteins and cells has also been reported .…”

“…The utilization of water washed plGFP@ZIF‐8 for cellular expression and gene delivery could also have an impact on uptake and efficiency. Since separate polymorphs of plGFP@ZIF‐8 can result on washing with water in place of ethanol tailoring of synthesis conditions to deliver the therapeutic gene in accordance to the requirements of individual cases, forms the basis of our future studies. It is expected that this approach will result in a promising gene delivery agent that protects and maintains functional activity of DNA and affords customized expression of genes leading to specifically designed persistence of therapeutic levels in vivo .…”

Phase Dependent Encapsulation and Release Profile of ZIF-Based Biocomposites

“…5b and c. The experimental data points were fitted with a logistic fitting function 64 which has previously been employed in the literature for the analysis of data related to the dissolution of different hydrophobic carries, including ZIF-8. 18,65,66 Among the biocomposites washed only with water, am and U13 showed the fastest dissolution: in 20 minutes, 100% of the encapsulated BSA was released (see ESI †) and the slowest release was measured for the dia topology: 100% of protein release was reached after 250 minutes. Whilst ZIF-C released 100% of the protein in 120 min.…”

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

“…[19][20][21][22][23][24][25][26][27] We and others have described a specific type of MOF called ZIF-8, 28, 29 composed exclusively of zinc metals interconnected by methylimidazole ligands, that crystallize "biomimetically" on a variety of biomacromolecules including soluble proteins, polysaccharides, viruses, and whole cells. [30][31][32][33][34][35][36] For this study, we used CFT073, a model urosepsis strain of UPEC frequently employed in the development of new vaccines. 37 Gram-negative E. coli has an outer membrane containing embedded polysaccharides and proteins, [38][39][40] which support ZIF-8 growth ( Figure 1C).…”