Multi-layered ZIF-coated cells for the release of bioactive molecules in hostile environments

Published on 01 August 2022Metal-organic framework (MOF) coatings on cells enhance viability in cytotoxic environments. Here, we show how protective multi-layered MOF bio-composite shells on a model cell system (yeast) enhance the proliferation of living cells exposed to hostile protease-rich environments via the dissolution of the shells and release of a protease inhibitor (antitrypsin).Lei Gan, Miriam de J. Velásquez-Hernández, Anita Emmerstorfer-Augustin, Peter Wied, Heimo Wolinski, Simone Dal Zilio, Marcello Solomon, Weibin Liang, Christian Doonan, and Paolo Falcar

Fabrication of 3D Oriented MOF Micropatterns with Anisotropic Fluorescent Properties

Published online: May 2, 2023Micropatterning crystalline materials with oriented pores is necessary for the fabrication of devices with anisotropic properties. Crystalline and porous metal–organic frameworks (MOFs) are ideal materials as their chemical and structural mutability enables precise tuning of functional properties for applications ranging from microelectronics to photonics. Herein, a patternable oriented MOF film is designed: by using a photomask under X-ray exposure, the MOF film decomposes in the irradiated areas, remaining intact in the unexposed regions. The MOF film acts simultaneously as a resist and as functional porous material. While the heteroepitaxial growth from aligned Cu(OH)₂ nanobelts is used to deposit oriented MOF films, the sensitivity to radiation is achieved by integrating a brominated dicarboxylate ligand (Br₂BDC) into a copper-based MOF Cu₂L₂DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane; L = BDC/Br₂BDC). The lithographed samples act as diffraction gratings upon irradiation with a laser, thus confirming the quality of the extended MOF micropattern. Furthermore, the oriented MOF patterns are functionalized with fluorescent dyes. As a result, by rotating the polarization angle of the laser excitation, the alignment of the dye in the MOF is demonstrated. By controlling the functional response to light, this MOF patterning protocol can be used for the microfabrication of optical components for photonic devices.Miriam de J. Velásquez-Hernández, Mercedes Linares-Moreau, Lea A. Brandner, Benedetta Marmiroli, Mariano Barella, Guillermo P. Acuna, Simone Dal Zilio, Margot F. K. Verstreken, Dmitry E. Kravchenko, Oliver M. Linder-Patton, Jack D. Evans, Helmar Wiltsche, Francesco Carraro, Heimo Wolinski, Rob Ameloot, Christian Doonan, and Paolo Falcar

Towards applications of bioentities@MOFs in biomedicine

Metal–organic frameworks (MOFs) combined with biomacromolecules, viruses and cells have emerged asnovel biocomposites for application to drug delivery, biosensing, biospecimen preservation, and cell andvirus manipulation. The integration of biological entities into MOF matrices generates MOF biocompos-ites with functional characteristics that cannot be observed in the separate components, such asenhanced chemical and thermal stability, resistance to proteases, MOF-conferred selectivity, and con-trolled release. In this review, we will discuss these functional properties and applications of the biocom-posites obtained by the encapsulation of (i) proteins, (ii) carbohydrates, (iii) nucleic acids, and (iv) virusesor cells in a MOF matrix. Finally, we review the post functionalization of MOF-based drug carriers withlipids as a potential route to enhance the dispersion, stability in biological fluids, and blood circulationtime of MOF-based drug delivery systems.Miriam de J. Velásquez-Hernández, Mercedes Linares-Moreau, Efwita Astria,Francesco Carraro, Mram Z. Alyami, Niveen M. Khashab ... et al

Phase dependent encapsulation and release profile of ZIF-based biocomposites

Biocomposites composed of Zeolitic Imidazolate Frameworks (ZIFs) are generating significant interest due to their facile synthesis, and capacity to protect proteins from harsh environments. Here we systematically varied the composition (i.e. relative amounts of ligand (2-methylimidazole), metal precursor (Zn(OAc)₂·2H₂O), and protein) and post synthetic treatments (i.e. washes with water or water/ethanol) to prepare a series of protein@ZIF biocomposites. These data were used to construct two ternary phase diagrams that showed the synthesis conditions employed gave rise to five different phases including, for the first time, biocomposites based on ZIF-CO₃-1. We examined the influence of the different phases on two properties relevant to drug delivery applications: encapsulation efficiency and release profile. The encapsulation efficiencies of bovine serum albumin and insulin were phase dependent and ranged from 75% to 100%. In addition, release profiles showed that 100% protein release varied between 40 and 300 minutes depending on the phase. This study provides a detailed compositional map for the targeted preparation of ZIF-based biocomposites of specific phases and a tool for the straightforward analysis of the crystalline phases of ZIF based materials (web application named “ZIF phase analysis”). These data will facilitate the progress of ZIF bio-composites in the fields of biomedicine and biotechnology.F. Carraro, M. de J. Velásquez-Hernández, E. Astria, W. Liang, L. Twight C. Parise, M. Ge, Z. Huang, R. Ricco, X. Zou, L. Villanova, C.O. Kappe, C. Doonan and P. Falcar

Modulation of metal-azolate frameworks for the tunable release of encapsulated glycosaminoglycans

Glycosaminoglycans (GAGs) are biomacromolecules necessary for the regulation of different biological functions. In medicine, GAGs are important commercial therapeutics widely used for the treatment of thrombosis, inflammation, osteoarthritis and wound healing. However, protocols for the encapsulation of GAGs in MOFs carriers are not yet available. Here, we successfully encapsulated GAG-based clinical drugs (heparin, hyaluronic acid, chondroitin sulfate, dermatan sulfate) and two new biotherapeutics in preclinical stage (GM-1111 and HepSYL proteoglycan) in three different pH-responsive metal-azolate frameworks (ZIF-8, ZIF-90, and MAF-7). The resultant GAG@MOF biocomposites present significant differences in terms of crystallinity, particle size, and spatial distribution of the cargo, which influences the drug-release kinetics upon applying an acidic stimulus. For a selected system, heparin@MOF, the released therapeutic retained its antithrombotic activity while the MOF shell effectively protects the drug from heparin lyase. By using different MOF shells, the present approach enables the preparation of GAG-based biocomposites with tunable properties such as encapsulation efficiency, protection and release.Miriam de J. Velásquez-Hernández, Efwita Astria, Sarah Winkler, Weibin Liang, Helmar Wiltsche, Arpita Poddar, Ravi Shukla, Glenn Prestwich, John Paderi, Pablo Salcedo-Abraira, Heinz Amenitsch, Patricia Horcajada, Christian J. Doonan and Paolo Falcar