Metal-organic frameworks (MOFs) have attracted widespread attention in the field of drug delivery due to their remarkable structural versatility and tunable properties. These materials, composed of metal ions or clusters coordinated to organic ligands, form one-, two-, or three-dimensional porous structures with high surface areas and controlled pore sizes. MOF is composed of metal ions, organic ligands and organic linkers. Among the three components that make up a MOF, the organic linker plays a crucial role in defining the architecture and functionality of the framework. One of the linkers, tetra-p-tolueneene (TPE), stands out due to its unique structural features and potential applications in drug delivery systems. The integration of TPE as a linker in MOFs not only enhances the stability and porosity of these frameworks but also imparts distinctive properties that can be harnessed for controlled drug release, making it an exciting area of research in pharmaceutical sciences. Tetra-p-tolylethene is a robust, conjugated organic molecule characterized by its rigid ethene core and four p-tolyl groups attached to the central ethene moiety. This configuration endows TPE with significant steric hindrance and electronic properties that are advantageous for constructing MOFs with high surface areas and large pore volumes. The p-tolyl groups provide additional hydrophobic interactions, enhancing the stability of the MOF structures in aqueous environments, which is crucial for biomedical applications. The conjugated system within TPE facilitates strong π-π interactions with various guest molecules, including drugs, thereby allowing for efficient loading and sustained release of therapeutics. The chemical versatility of TPE enables the fine-tuning of MOF properties through functional group modifications, thereby optimizing the drug delivery performance for specific applications.
Figure 1. Metal-organic framework (MOF) structures. (Kampouraki ZC, et al.; 2019)
TPE-based MOFs exhibit multiple advantages in drug delivery, including improved drug bioavailability, targeting, and controlled release capabilities. MOFs constructed with TPE joints can be used to encapsulate a variety of drugs, ranging from small molecules to large biomolecules, which can avoid premature drug degradation and enhance the stability of the encapsulated drugs. The porous nature of these MOFs gives them high drug loading capacity and the potential for co-delivery of multiple therapeutic agents, which is beneficial for the treatment of a variety of complex diseases. In addition, the functional groups on TPE can also be customized to interact with specific biological targets, thereby facilitating targeted drug delivery to specific tissues while minimizing systemic toxic side effects. This drug delivery system can not only improve the therapeutic efficacy but also reduce the risk of side effects, making TPE-based MOFs a promising platform for advanced drug delivery systems. To gain insight into the benefits of TPE-based MOFs, one must consider their synthetic and structural properties. TPE-MOF can be prepared by a solvothermal method, in which TPE and metal salts are dissolved in a solvent and synthesized under high temperature and pressure conditions. This process can form a crystalline framework with well-defined pore sizes. The choice of metal ion, such as zinc, copper, or zirconium, can further influence the properties of the resulting MOF, allowing the pore size and shape to be tailored to suit different drug molecules. The crystalline nature of these frameworks not only contributes to their thermal and chemical stability but also ensures reproducibility of drug loading and release profiles, which is crucial for clinical applications.
In terms of drug loading, TPE-based MOFs offer several mechanisms for encapsulating therapeutic agents. Drugs can be physically adsorbed onto MOF surfaces, trapped within pores, or chemically bound to the scaffold. The high surface area and porous structure of TPE-based MOFs enable them to accommodate large amounts of drug molecules, thereby increasing the therapeutic payload. In addition, the hydrophobicity of TPE p-tolyl groups can interact with hydrophobic drugs to improve their solubility and stability within the MOF structure. This is particularly beneficial for poorly soluble drugs, which often face challenges in achieving adequate bioavailability. TPE-MOF can also be modified to achieve controlled release of loaded drugs, which is another significant advantage and can be achieved through various stimulus-response mechanisms. Release of the encapsulated drug can be triggered by changes in pH, temperature or the presence of specific enzymes, often characteristic of the target disease environment. For example, in the acidic environment of a tumor, the acidic pH can induce degradation of the MOF structure, thereby releasing the drug directly at the tumor site. This targeted release not only maximises therapeutic efficacy, but also minimises systemic distribution of the drug and reduces potential side effects. Moreover, the biocompatibility and biodegradability of TPE-based MOFs are essential considerations for their application in drug delivery. Studies have shown that MOFs incorporating TPE linkers exhibit minimal toxicity and are well-tolerated by biological systems. Upon fulfilling their drug delivery function, these MOFs can degrade into non-toxic components that can be easily eliminated from the body. This ensures that the use of TPE-based MOFs does not introduce long-term toxicity or adverse reactions, which is a critical requirement for any drug delivery vehicle. Furthermore, the versatility of TPE-based MOFs extends beyond conventional drug delivery applications. These frameworks can be engineered to carry genetic material, such as DNA or RNA, for gene therapy, or to deliver imaging agents for diagnostic purposes. The ability to simultaneously load and deliver multiple types of therapeutic agents or combine therapeutic and diagnostic functions (theranostics) makes TPE-based MOFs an attractive option for personalized medicine. By tailoring the properties of TPE-based MOFs to the specific needs of the patient and the disease, it is possible to achieve more effective and personalized treatment outcomes.
Alternate Names:
Tetra-p-tolyl ethylene
1,2-Bis(p-tolyl)ethene
1,2-Bis(4-methylphenyl)ethylene
References:
1. Kampouraki ZC, et al.; Metal Organic Frameworks as Desulfurization Adsorbents of DBT and 4,6-DMDBT from Fuels. Molecules. 2019, 24(24):4525.
2. Wang Y, et al.; Metal-organic frameworks for stimuli-responsive drug delivery. Biomaterials. 2020, 230:119619.
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