Application of Metal-Organic Framework (MOF) Nano-Drug Carriers in Biomedicine

Metal-Organic Frameworks

Metal-organic frameworks (MOFs) form an extended and infinite network of 1D/2D/3D MOFs with inorganic metal (e.g., transition metal and lanthanide metal) ions/clusters as nodes and organic ligands (e.g., carboxylates, phosphonates, imidazolates, and phenolates) as supports. In recent years, the application of MOFs in the biomedical field has received increasing attention. When the size of MOF particles is reduced to the nanoscale, these nano-MOFs (NMOFs) can be used as drug delivery carriers for imaging, chemotherapy, photothermal therapy, or photodynamic therapy.

Compared with other porous materials, MOFs have several outstanding advantages:

(1) High specific surface area and porosity for high loading of therapeutic drugs.

(2) Easy modification of the physical (e.g., pore size and shape) and chemical properties of MOFs by inorganic clusters and organic ligands. In addition, desired functional groups can be added to organic ligands through pre-design or post-synthesis modification methods of the ligands.

(3) The open windows and pores of MOFs allow for the interaction of diffusing matrices with the binding molecules.

(4) Moderately strong ligand bonds make MOFs biodegradable.

(5) A well-defined structure facilitates the study of host-guest interactions. Due to these unique properties, MOFs are considered among the best candidates for drug delivery and cancer therapy.

The Functionalization of Drug Delivery

MOFs possess unique properties, such as highly ordered structures, high surface area, and large pore volumes, enabling them to adsorb functional molecules on their external surface or open channels and trap these molecules within the framework. Additionally, functional molecules can be synthesized via a one-pot method or post-synthetically modified, and they can be covalently bound to MOFs. There are four main advanced strategies for functionalizing MOFs with therapeutic agents for biomedical applications, including surface adsorption, pore encapsulation, covalent binding, and functional molecules serving as building blocks .

Applications in Drug Delivery

A major problem with conventional chemotherapy is the need to use high doses of drugs due to poor biodistribution, leading to frequent dose-related side effects. This calls for the exploration of novel and efficient drug delivery systems (DDSs). Recent studies have shown that the application of MOF nanocarriers enables targeted drug delivery, increased cellular uptake, and controlled drug release, making MOFs a promising class of drug-releasing DDSs, including anticancer drugs, antimicrobials, metabolic marker molecules, antiglaucoma drugs, and hormones.

Drugs

Typically, drugs are loaded into MOFs via in situ encapsulation or post-synthesis modification strategies. The former is a relatively simple method for heat-stabilized drugs to overcome premature drug release. The latter provides a milder environment to avoid damaging the drug molecule. With the development of MOF chemistry, a range of MOFs have been explored as promising candidate carriers for applications in this field.

Nucleic Acids

Nucleic acids include deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids play an important role in the storage and expression of genetic information. Overall, the incorporation of nucleic acids into MOFs nanocarriers prevents their degradation and accelerates their cellular uptake. In addition, surface modification of MOFs nanoparticles with nucleic acids can improve their colloidal stability by providing spatial site resistance and electrostatic depolymerization. Currently, MOFs have been investigated for the delivery or controlled release of DNA, small interfering RNA (siRNA), and nucleic acid aptamers.

Protein

Proteins have many functions, such as DNA replication, catalysis of metabolic reactions, and molecular transport. Due to their large size, charged surface, and environmental sensitivity, proteins have difficulty in naturally crossing cell membranes without losing their structural integrity. To exploit proteins for therapeutic purposes, MOFs nanoparticles for intracellular delivery of proteins have attracted increasing attention in recent years.

Despite the remarkable achievements in the application of MOFs in the field of drug delivery, there are still some challenges in this field, such as the potential toxicity of MOF-based DDS for clinical applications. To reach the clinical application of MOF nanoparticles, the performance of MOFs-based DDS for preclinical evaluation should be optimized through systematic in vivo studies on their stability, degradation mechanism, and side effects on normal organs.

References

1. Jeyaseelan C.; et al. Metal organic frameworks: An effective application in drug delivery systems. Inorganic and Nano-Metal Chemistry. 2022, 52(12): 1463-1475..
2. Miri B.; et al. Application of a nanoporous metal organic framework based on iron carboxylate as drug delivery system. Iranian Journal of Pharmaceutical Research: IJPR. 2018, 17(4): 1164.