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.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.