Unlocking the Potential of Metal-Organic Frameworks in Discovery

The Nobel Prize-winning scientists who created these highly porous networks have identified materials with the potential to enhance the targeted delivery of drugs and even contribute to advances in X-ray crystallography

Metal-organic frameworks (MOFs)—the genius technology behind the 2025 Nobel Prize in Chemistry— have immense potential for addressing a diverse range of critical challenges. Some of the promising areas of development in MOF research include applications in the drug discovery arena that are particularly relevant to the work that Charles River does.

The Nobel Prize was awarded last month to Susumu Kitagawa, Richard Robson, and Omar M. Yaghi for the development of MOFs, which are crystalline materials comprised of metal ions or clusters that act as “nodes”, connected by organic molecules that act as “linkers”. Together, they can create highly porous, regular networks that have large internal surface areas and cavities. This architecture enables materials to trap, store, release, or interact with molecules in a controlled manner, leading to potential applications in areas as diverse as harvesting water from the air, capturing carbon dioxide, or storing toxic gases.

The unique properties of MOFs offer intriguing possibilities for their use in drug discovery. Their high surface areas and porosity provide large numbers of adsorption sites and an extensive internal space for the incorporation of molecules, making MOFs an attractive platform for the delivery of drugs. Combined with the ability to tune the pore size and functionalise the structures, very high drug loading can be achieved, surpassing that of other drug carrier technologies. The ability to tune the architecture of the MOF through the choice of metal ion and organic ligand allows for drugs with different sizes and physicochemical properties to be accommodated, whilst the choice of architecture and ability to modify the structure offer opportunities to control the release of the drug molecule, for example, to allow sustained release.

MOFs can be designed to enable the targeted delivery of drugs, for example, by designing frameworks that are degraded at low pH, by enzymes that are overexpressed in diseased cells, or by an external light source. It is even possible to design MOFs to be responsive to magnetic fields. Their properties also make them ideal as carriers to deliver drugs to the lungs in dry powder inhalers. Encapsulation of a molecule in a MOF can be used to overcome poor properties that can limit the effectiveness of, or result in the failure of, potential drug molecules, such as low aqueous solubility, poor stability, or low bioavailability.

In addition to the delivery of drug molecules, MOFs have potential applications in other areas of drug discovery. For example, their use in biosensing has been investigated whereby a fluorescent probe can be released upon the binding of a target to the system. MOFs can also be used in the analysis of drug molecules by trapping them in an orderly fashion, allowing X-ray or microcrystal electron diffraction structures to be generated. This technology can enable the generation of structures where traditional crystallization methods have failed and can facilitate the creation of structures from very small quantities of drug molecules.

Whilst there are several potential uses of MOFs in drug discovery, challenges remain to be addressed. The synthesis of MOFs needs to be optimized to ensure that they can be produced at scale, at a reasonable cost, with high batch-to-batch reproducibility. Any variability in crystal size and pore size distribution could have a significant impact on the compound loading and release characteristics. If MOFs are to be used for the delivery of drug molecules, it is essential that they are demonstrated to be safe, as the release of metal ions and organic degradation products could lead to toxicity. Whilst some toxicological data is available for MOFs, further research is needed to study the long-term safety of these materials.

If further research can surmount these outstanding obstacles, then the future may see MOFs being exploited more fully in the development and delivery of drug molecules.