Metal-organic Frameworks and Novel Drug-Carrying Systems

Metal-organic frameworks (MOFs) form long-range ordered geometric structures through the coordination and binding of metal ions and small organic molecules, changing metal elements and small organic molecules, resulting in an ever-expanding family of MOFs. Due to their excellent properties such as low density, high specific surface area, high porosity, tunable pore size and morphology, and topological diversity, MOFs have broad application prospects in the field of drug delivery. As a drug carrier, MOFs can not only protect the drug, but also improve the human body’s absorption, release and metabolism of the drug, and enhance the therapeutic effect of the drug, which has potential advantages.

Introduction to MOFs

In 1995, Yaghi et al. discovered a new porous material that had a lasting impact on the fields of chemistry, biology, physics, and materials science. These materials, named metal-organic frameworks or porous coordination polymers, differ from traditional inorganic porous materials and from general organic complexes. MOFs are a class of crystalline porous hybrid materials with periodic network structure formed by the coordination self-assembly of metal centers and bridging organic ligands. Depending on the connection design formed by the initial metal clusters, the skeleton structure itself can extend infinitely in any direction. The initial backbone will expand into a polymer-type structure, forming a porous sponge-like material that includes pores and channels. The porosity of MOFs is defined as the ability to maintain a porous structure without guest molecules in the pores. This means that when all guest molecules are removed under vacuum, the pores do not collapse, which can lead to permanent porosity. Through the encapsulation strategy, researchers have been able to expand the MOF family with complex, highly tuned, rationally designed structures and are working towards the development of a comprehensive multifunctional MOF platform.

MOFs Material Classification

MOFs materials are constructed by interconnecting secondary structural units and organic linkers. Different types and configurations of MOFs materials can be realized by choosing different metal centers and organic ligands. MOFs are mainly classified into the following two categories. (1) According to the different classification of metal nodes: zinc-based, iron-based, zirconium-based, copper-based, titanium-based, chromium-based and MOFs materials containing other metals. (2) According to different types of configuration sources: MIL-MOFs (MIL), ZIF-MOFs (ZIF), UiO-MOFs (UiO), PCN-MOFs (PCN) and other configuration MOFs.

MOFs Materials and Drug Loading Methods

Individual differences lead to insufficient drug delivery to the lesions, and the need to use high doses of drugs is a major problem with traditional chemotherapy. Therefore, there is an urgent need to develop novel and efficient drug delivery systems. MOFs have been developed as a promising class of drug delivery systems for loading anticancer drugs, proteins, antibodies, and small-molecule drugs for the treatment of other diseases. Studies have shown that applying some new encapsulation strategies, such as the previously reported one-pot synthesis method, encapsulates drugs into MOFs, and delivers drugs to specific microenvironments through a pH-responsive MOFs drug delivery platform to trigger drug release, which can overcome the problem of premature drug release.

Figure 1. Metal-organic frameworks for advanced drug delivery.
Due to their extremely large surface area, easy surface modification, and tunable porous structure, MOFs are regarded as ideal nanocarriers for loading various drugs. Typically, drugs are loaded into MOFs through in situ encapsulation or post-synthesis modification strategies. In situ encapsulation is simpler than post-synthesis modification, and is suitable for heat-resistant drugs to solve the premature release of drugs. Although the post-synthetic modification strategy is more complex and time-consuming, its synthesis conditions are milder and can avoid the destruction of drug molecules. With the continuous development of MOFs, a series of MOFs have been developed as promising nanocarriers for drug delivery.

Zeolitic imidazolium frameworks (ZIFs) are a class of MOFs that can be used as drug carriers. The representative of ZIFs is ZIF-8. ZIF-8 is a large cavity with a diameter of 11.6A formed by the coordination of 2-methylimidazolium and zinc ion tetrahedra, and there are small openings of 3.4A between the cages. Window crystal material. ZIF-8 has high thermal stability, good biocompatibility, high drug loading rate, and pH responsiveness, which can respond to the weakly acidic environment associated with various diseases such as malignant tumors, and is a promising pH-responsive drug delivery vector.

MIL-101(Fe) is a typical example of nontoxic porous iron (III)-based MOFs, zeolite-type MOFs composed of metal octahedra and trimers of 1,4-benzenedicarboxylic acid. The MOFs have large specific surface area and tunable pore size, and have great application prospects in high drug loading and sustained release.