Delivery of Immobilized IFN-γ With PCN-333 and Its Effect on Human Mesenchymal Stem Cells.

Interferon-gamma (IFN-γ) plays a vital role in modulating the immunosuppressive properties of human mesenchymal stem/stromal cells (hMSCs) used in cell therapies. However, IFN-γ suffers from low bioavailability and degrades in media, creating a challenge when using IFN-γ during the manufacturing of hMSCs. Metal-organic frameworks (MOFs), with their porous interiors, biocompatibility, high loading capacity, and ability to be functionalized for targeting, have become an increasingly suitable platform for protein delivery. In this work, we synthesize the MOF PCN-333(Fe) and show that it can be utilized to immobilize and deliver IFN-γ to the local extracellular environment of hMSCs. In doing so, the cells proliferate and differentiate appropriately with no observed side effects. We demonstrate that PCN-333(Fe) MOFs containing IFN-γ are not cytotoxic to hMSCs, can promote the expression of proteins that play a role in immune response, and are capable of inducing indoleamine 2,3-dioxygenase (IDO) production similar to that of soluble IFN-γ at lower concentrations. Overall, using MOFs to deliver IFN-γ may be leveraged in the future in the manufacturing of therapeutically relevant hMSCs.

Differential sensitization toward lanthanide metal-organic framework for detection of an anthrax biomarker.

A novel Tb-doped Eu-based metal-organic framework (Eu-MOF@Tb) has been developed by incorporating hexanuclear europium cluster and 2,2'-bipyridine-5,5'-dicarboxylic acid as well as coordination with Tb(III). Owing to the diverse coordination status of Tb(III) and Eu(III) in MOF, antenna effect emission from Tb(III) can be invoked by dipicolinic acid (DPA), but the luminescence originating from Eu(III) remains unchanged. Taking advantage of this phenomenon, a ratiometric luminescent method for detection of DPA, a biomarker for Bacillus subtilis spores, was developed through differential sensitization toward lanthanide ions. This analysis method allowed for the detection of DPA in the 0.2-10 µM concentration range, with a detection limit of 60 nM. It was further validated by spiked recoveries (89.3-110%) of real-world samples with RSD values in the range 3.9-11%. Alongside this, a paper indicator test was prepared for naked-eye detection of DPA via a dose-sensitive color evolution from red to green under UV light. The effectiveness of the proposed approach was explored in the detection of bacterial spores in real biological and environmental samples and indicated great potential for applications as a real-time monitoring system against the anthrax threat.

Catalytic Activity, Stability, and Loading Trends of Alcohol Dehydrogenase Enzyme Encapsulated in a Metal-Organic Framework.

Recently, it has been shown that enzyme encapsulation inside metal-organic frameworks (MOFs) can increase enzyme activity and serve as protection from adverse environmental conditions. Little is understood about how the enzymes move into and are held inside the MOFs although it is believed that intermolecular forces between the MOF and the enzyme cause it to be held in place. If this process can be better understood, it can have dramatic implications on the cost-effectiveness and implementation of enzyme-MOF complexes. This is of specific importance in the medical sector for protein therapy and the industrial sector where enzyme use is expected to increase. Herein, we synthesized alcohol dehydrogenase (ADH) and PCN-333 to study encapsulation, stability, and enzyme activity to expand the knowledge of our field and offer a potential improvement to a synthetic route for biofuel synthesis. From this, we found a correlation between the concentration of a buffer and the loading of an enzyme, with surprising loading trends. We conclude that the buffer solution decreases interactions between the enzyme and MOF, supporting conventional theory and allowing it to penetrate deeper into the structure causing higher enzyme loading while allowing for excellent stability over time at various pH values and temperatures and after multiple reactions. We also observe new trends such as a rebounding effect in loading and "out-of-bounds" reactions.