Metal-organic frameworks (MOFs) are already making names for themselves in next-generation storage and separation of specialty chemicals, with the transition to commercial scales. But their unique chemistry has also made them attractive to a wide range of other applications in biotechnology. As of mid-2019, more than 1,000 academic papers have been published on the potential biomedical applications of MOFs. These applications lean on the traditional strengths of MOFs, including their ability to selectively store and separate molecules with high capacity. These capabilities are valuable in the pharmaceutical industry for drug delivery: MOFs provide a unique opportunity for re-inventing the landscape for life-saving medications.
Properties that matter
Encapsulating therapeutics in nanotechnology is a leading area of in vivo research and development within biotechnology, as nanoparticles can transport drugs into various cell types. MOFs, a group of nanoporous materials, are emerging as an ideal category of nanoparticles for this task. MOFs have unique properties that can be highly tuned for in-vivo applications:
- A versatile range of sizes
- Higher storage capacity than other nanoporous materials
- Good biocompatibility and stability
- Surface functionalization that enables the release of drugs under specific conditions
Size: Firstly, the delivery of drugs inside MOFs requires the MOF to sized appropriately for in-vivo applications. Particle size has a direct impact on cellular uptake and the ability of a material to be circulated throughout the body. MOFs can be synthesized across a range of length scales from the centimeter down to the critical nanometer scale, which gives them the potential to be used in a range of in-vivo applications.
Capacity: At the same time, the nanoparticles must have a high loading capacity of the targeted drug to make the treatments effective for their intended targets. In conventional nanomaterials currently used in biopharma applications, the external surface of the nanoparticle is utilized to store and deliver drugs. However, MOFs possess a high internal surface area that can be leveraged in conjunction with their external surface area to store and deliver a higher amount of the active drug.
Biocompatibility and stability: Importantly, any solution for in vivo drug delivery must be biocompatible and stable. Several toxicity studies have indicated that certain MOFs do not harm the organism that ingests them. The toxicity of a MOF is dictated by the organic ligands and metal nodes that the MOF is constructed from, and a wide range of biocompatible MOF ligands and metals are available. Additionally, MOFs can be synthesized to be stable under biological conditions. This stability allows MOFs to get to the targeted areas of an organism without breaking down.
Surface functionalization: Finally, MOFs are uniquely tunable, allowing them to be tailored to specific drug delivery requirements, such as targeted or extended-release of drug cargos. This tailorability is a result of the flexibility of the MOF synthesis. The metal nodes or organic linkers of the MOF can be functionalized using coordination chemistry or covalent chemistry, respectively. Additionally, the electrostatics of the external MOF nanoparticle surface can be controlled during the synthesis allowing for electrostatic interactions of MOFs to be utilized to attach molecules to the MOF synthesis. By controlling the external surface of the MOF, functionality can be added to control the release of drugs or allow for the MOF particle to have a high affinity for a certain affected area.
MOFs are uniquely tunable, allowing them to be tailored to specific drug delivery requirements, such as targeted or extended-release of drug cargos.
From diabetes to cancer
Using MOFs, researchers have created a range of immobilized enzyme systems that can be tuned to various therapeutic applications. Taking advantage of the unique pore systems that can be engineered within the materials it is possible to prevent enzyme denaturing or aggregation once loaded into a MOF. This feature is critical in finding effective new ways to treat diabetes patients, a continuing challenge in biotechnology.
Millions of diabetics manage their blood sugar by using direct insulin injections, which are both painful and inconvenient. Oral delivery of insulin has been challenging because pepsin in the gut can degrade the insulin before it reaches its target. MOFs offer a potential solution.
Scientists at Northwestern University have encapsulated insulin in a MOF, which prevented insulin from degrading. The MOF provides a stable scaffolding that prevents pepsin from attacking and degrading the MOF. Furthermore, the MOF structure enabled high loadings of insulin and showed the capability for a controlled release under simulated physiological conditions.
In another set of work, scientists showed that MOFs can be used to deliver anticancer drugs and painkillers, as well as combination drugs. MOFs can improve release profiles of the targeted drug, increase the availability of the drug at a target site, and allow for drugs to be delivered in tandem with other active agents. For example, scientists used MOFs to lowerthe amount of active drug required in cancer treatments.
Scaling to the clinic
MOFs show great promise in the drug delivery applications, but more work is necessary to take them into practice. To date, research into the biological applications of MOFs has been overwhelmingly limited to milligram quantities in academic laboratories, with the exception of one Phase 1 clinical trial involving a MOF-encapsulated drug to treat advanced tumors. However, just like in other areas, MOFs in biology may be poised to transition from academic novelties to commercial products.
Researchers have already done fundamental work on toxicity, size control, and stability carried out, as well as work on specific applications. What remains is further development and testing of specific MOFs tailored to specific applications, paired with clinical testing.
This progress, coupled with the ability to now synthesize MOFs at ton scale, will undoubtedly move MOFs closer to the clinic. At NuMat, we are excited to help bring MOFs to an ever-expanding range of possibilities for biotechnology. In conjunction with partners, NuMat is leading from the front in launching a pipeline of pre-clinical programs. We are developing integrated solutions for MOFs that will reinvent how medicine is delivered to those who need it most.
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