The Metal–Organic Framework & Its Biomedical Future

How can we alter the mechanism of medicine release? Is there a way to make regular intake of medication no longer a nuisance?

For centuries, experts in all fields have been researching methods to increase the efficiency of drug delivery. By synthesizing components, scientists made many attempts to adjust the porosity and specific surface area of the material.

From the 1960s to the 1990s, a surge of novelty and breakthroughs was followed by the debut of the metal organic frameworks.With both high porosity, specific surface area, and stability, this multi-dimensional material inspired scientists to implement it into biomedicine.

Investigations show that utilizing metal organic frameworks will potentially serve as a new approach to medication and prevention of potential diseases or medical risks. Its viability in drug delivery depends on multiple aspects of the MOFs’ internal constituents and structure. In the following text, elaborations on the MOFs’ biomedical advantage regarding drug loading, drug release, and biocompatibility will be presented along with corresponding evidence.

MOFs have frequently been proven to be an efficient complement to the current medical field. By synthesizing the unique and competent properties mentioned above, MOFs possess tremendous potential in delivering drugs that can mitigate the side effects or medical risks of currently prevalent medications. Although biochemical research suggests a promising future for MOFs, the material still needs to undergo testing and clinical trials before they can be implemented in actual therapies. These testings will then concern the biocompatibility of the MOFs, soliciting analysis of their components that prospectively contributes to their toxicity.

II. Considering the impacts of different factors on toxicity

The MOFs' varying chemical construction can lead to different levels of toxicity, which affects their ability to deliver medication. Two of the most decisive components that determine the biocompatibility of an MOF are the metals used as well as the size of the particles.

To begin with, the type of metal used can affect the biosafety of the MOFs, thus influencing their viability in real therapies. While there are general toxicity rankings of conventionally used metals, scientists are still unable to develop an accurate and confident calculation of the metals’ exact toxicity level. According to the Chemical Engineering Journal, copper and manganese are highly toxic; zinc, iron, copper, and aluminum are less toxic; chromium, zirconium, and magnesium are the safest. Though this generalized ranking of the commonly seen metals in MOFs is tested and reasonable, discrepant conclusions are drawn in other existing experiments. As elaborated in Àngels Ruyra’s Synthesis, culture medium stability, and in vitro and in vivo zebrafish embryo toxicity of metal-organic framework nanoparticles, copper and manganese turn out to be the most toxic, while magnesium remains the safest. Paulinaap Wiśniewska mentioned that MOFs consisting of copper induce the synthesis of hemoglobin, superoxide anions, and hydroxyl radicals, causing inevitable hemolysis. This is an urgent issue for MOFs because they will certainly come in contact with blood and intestinal tissues.

Based on the explanation above, it seems like the toxicity of MOFs is capricious and highly unpredictable, making it very unlikely to be a candidate for optimizers of modern medication methodology. While this dilemma of toxicity presents dangers of using the material in medical treatments, the toxicity of some metals, including copper and zinc, can be reduced or recovered within seventy-two hours after consuming and removing the MOFs. Thus, future methods or material choice may need to consider the reduction of toxicity (which will be explored later in the text).

Moreover, particle size significantly affects MOFs’ level of toxicity. Smaller particles, especially particles reduced to the nanoscale, have an extremely high efficiency and medical productivity due to their efficacy in high penetration and manipulation of drug release. Smaller particles can travel with ease through membranes and body systems, while particles with a larger size fail to permeate. Larger particles can be dangerous and cause potential harm to the human body because of their large surface area and chemical reactivity. With this in mind, smaller particles are safer and more suitable for biomedical applications.

Furthermore, particles of smaller size can facilitate medication in cases where high penetration of medicine is required. According to researcher Dongban Duan's 2018 study, smaller particles can be helpful when it comes to eliminating cancer cells. Since smaller particles move and penetrate more easily, they have a higher cytotoxicity, followed by releasing more drugs and accumulating at the site of the tumor. MOFs with aggressive behavior are highly effective in cancer treatment, as the cancer cells themselves are obstinate.

III. Reducing the toxicity of MOFs: surface coating

While the metallic components and the particle size of the MOFs dominantly govern their toxicity, methods or materials have been developed and discovered to neutralize their harms and make them feasible for modern medical uses. As MOFs inevitably contact the surface of cells, they can release toxins through the interaction between themselves and the bloodstreams. One of the dominant ways of modifying the surface of MOFs is to coat the material with biomolecules, lowering the overall toxicity and decreasing the chances of the toxic surface coming in contact with human systems.

According to Tania Hidalgo et al.'s 2018 study, coating MOFs with chitosan. By coating this biomaterial on MIL-100, increased chemical stability is observed. As mentioned in the former text, higher chemical reactivity, common in many larger particles, can be dangerous and toxic. With a more stable level of reactivity, MIL’s toxic level can be maintained and even lowered. Additionally, the addition of chitosan makes the material less prone to forming inflammatory cytokines. The presence of inflammatory cytokines is not always considered as a sign of the body’s declining health, instead, it is initially a helpful component of the body. It communicates with proteins and implies that the immune cells are protecting the body by fighting invasive cells. Yet, to a certain extent, the opposite effect is achieved. Bare MIL without any biomaterial coating can increase the inflammatory cytokines and thus cause overly aggressive immune cells. This phenomenon may lead to severe diseases, including low blood pressure, organ failure, type 2 diabetes, strokes, and tumor growth. In this case, the chitosan layer avoids the occurrences of this issue and provides a more balanced state for the immune system.

To sum up, assessing MOFs’ level of biocompatibility and toxicity is a critical first step for the material to be potentially implemented in medications. Utilizing different metals as part of the material and adjusting the particles to various sizes greatly influences the toxicity of MOFs. Despite latent toxins in the material, methodologies like biomaterial coating are developed to neutralize and alleviate the impact of MOFs’ toxicity.