Continuous‐Flow Synthesis of ZIF‐8 Biocomposites with Tunable Particle Size

Abstract

Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, the progress in this research area is based on laboratory batch methods. Now, the first continuous flow synthetic method is presented for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1‐antitrypsin, AAT) in ZIF‐8. The in situ kinetics of nucleation, growth, and crystallization of BSA@ZIF‐8 were studied by small‐angle X‐ray scattering. By controlling the injection time of ethanol, the particle growth could be quenched by ethanol‐induced crystallization from amorphous particles to ZIF‐8 crystals. The particle size of the biocomposite was tuned in the 40–100 nm range by varying residence time prior to introduction of ethanol. As a proof‐of‐concept, this procedure was used for the encapsulation of AAT in ZIF‐8. Upon release of the biotherapeutic from the composite, the trypsin inhibitor function of AAT was preserved.

Stabilization of Supramolecular Membrane Protein-Lipid Bilayer Assemblies Through Immobilization in a Crystalline Exoskeleton

“…Kinetics of nucleation, particle growth, 38 crystallization, and the morphology of the particles were investigated in situ via synchrotron-based small-angle and wide-angle X-ray scattering (SAXS/WAXS) techniques. 42,43 We investigated four different samples (20×16 Lp@ZIF, 20×16 ZIF-L, 40×16 Lp@ZIF, and 40×16 ZIF-L) using a stopped flow device to initiate the rapid mixing of the reagents (mixing time <100 ms). See the SAXS section of the SI for full experimental details.…”

Metal‐Organic Frameworks: A New Platform for Enzyme Immobilization

“…For example, microfluidics-assisted encapsulation was proposed to synthesize nanoZIF-8 biocomposites that are suitable for intracellular delivery. [26] Qu et al have developed an erythrocyte membranecloaked MOF-based biomimetic nanoreactor encapsulating GOx and the prodrug tirapazamine (TPZ). [34] In vitro and in vivo outcomes indicated that this biomimetic nanoreactor could enter tumors.…”

“…In addition, another report by Falcaro's group was indicated that continuous flow synthesis of proteins@ZIF-8 biocomposites in a microfluidic setup enable to controlled the particle size of proteins@ZIF-8 in the 40 to 100 nm range. [26] This microfluidicassisted encapsulation method was then applied to the synthesis of α1-antitrypsin@ZIF-8 biocomposite with the size suitable for intravenous drug delivery applications.…”

Recent Progress on Defect‐rich Transition Metal Oxides and Their Energy‐Related Applications

“…Defects are deviations from the periodic structure in the crystal. The destruction of the crystal structure will lead to new properties of the electronic structure, which is different from that in the perfect crystals [30–33] . At the same time, the defects in crystals will also cause the redistribution of electron density, thereby increase the binding energy of metal oxides and metal atoms.…”

“…The destruction of the crystal structure will lead to new properties of the electronic structure, which is different from that in the perfect crystals. [30][31][32][33] At the same time, the defects in crystals will also cause the redistribution of electron density, thereby increase the binding energy of metal oxides and metal atoms. Therefore, the defects in catalysts will tune the reaction surface/interface properties, the electronic structures, the reaction path and the free energy of reactant adsorption.…”