Zeolitic Imidazolate Framework Nanoencapsulation of CpG for Stabilization and Enhancement of Immunoadjuvancy

Metal-organic frameworks (MOFs) have been used to improve vaccine formulations by stabilizing proteins and protecting them against thermal degradation. This has led to increased 2 immunogenicity of these proteinaceous therapeutics. In this work we show that MOFs can also be used to protect the ssDNA oligomer, CpG, to increase its immunoadjuvancy. By encapsulating phosphodiester CpG in the zinc-based MOF, ZIF-8, the DNA oligomer is protected from nuclease degradation and exhibits improved cellular uptake. As a result, we have been able to achieve drastically enhanced B-cell activation in splenocyte cultures comparable to the current state-of-the-art, phosphorothioate CpG. Furthermore, we have made a direct comparison of micro- and nano-sized MOF for the optimization of particulate delivery of immunoadjuvants to maximize immune activation

Carrier Gas Triggered Controlled Biolistic Delivery of DNA and Protein Therapeutics from Metal-Organic Frameworks

Abstract: The efficacy and specificity of protein, DNA, and RNA-based drugs have made them popular in the clinic; however, their susceptibility to environmental stressors adds significant challenges to formulating biomacromolecules into delivery systems where the kinetics of release can be tuned. Further, these drugs are often delivered via injection, which requires skilled medical personnel and produces biohazardous waste. Here, we report an approach that allows for the controlled delivery of DNA and protein therapeutics to allow for either burst or slow-release kinetics without altering the formulation; further, we show we can deliver these materials into the tissues of very different organisms without the use of needles. We show that biomaterials encapsulated within the highly porous metal-organic Framework ZIF-8 are stable as a powder formulation that can be shot into tissue with a low-cost gas-powered “MOF-Jet” for direct delivery into living tissues of plants and animals and the release of the biomaterials can be controlled by judiciously choosing the compressed gas used in the gun. Many MOFs, including ZIF-8, are acid labile and readily dissolve at low pH. When CO2 is used as the carrier gas to shoot MOFs into moist tissue, we show that we can create a transient and weakly acidic local environment that causes the near-instantaneous release of the biomolecules. Conversely, when air is used, the MOF is delivered into tissue and degrades slowly over a week, releasing biomolecules. This innovation represents the first example of biolistic-mediated controlled delivery of biomolecules with ZIF-8 and provides a powerful tool for fundamental and applied plant and animal sciences research