Nanotherapy

Nanoparticles, Research, Advantages and Challenges


Introduction


Nanotherapy is a branch of nanomedicine that involves using nanoparticles to deliver a drug to a given target location in the body so as to treat the disease through a process known as targeting.

Compared to the conventional methods, this method has gained more popularity because it promises high precision when it comes to administering therapeutic formulations.





With conventional chemotherapy, there is no targeting, which means that the drug is simply transported by the circulatory system until it reaches and acts upon the affected body part. In the process, the drug is likely to be affected by various molecules or react with other compounds. As a result, this method has been found to present various problems especially when treating cancer. However, with nanotherapy, the carrier is protected from such degradations, which allows it to reach given target cells in the body for a local reaction.


How Nanotherapy Works


Much of the research in nanotherapy has been largely directed towards cancer therapy. One of the biggest issues with conventional methods is that as the drug product is distributed throughout the body, both healthy and unhealthy (cancerous cells) are affected, which in turn affects the effectiveness of cancer treatment. It is for this very reason that most cancer patients tend to be hesitant when it comes to chemotherapy.

It is worth noting that while drug products help in the treatment process, they also cause toxic effects on the healthy cells, causing patients to present a variety of symptoms. However, nanotherapy, which is also referred to as targeted therapy, offers to deliver the molecules to the affected cells in order to help treat the disease without causing other negative effects to the healthy cells.

One of the biggest advantages of nanoparticles used is that they have a larger surface area, which allows for multiple functional groups to be added to the surface. Each of the functional groups contributes to the effectiveness of this method of therapy.

There size is also a big advantage with regards to elimination. For instance, a good number of studies have shown that nanoparticles of between 10nm and 100nm are ideal for nanotherapy.

Whereas nanoparticles that are less than 10nm are rapidly eliminated through the kidneys, those larger than 10nm are easily eliminated through the immune system. These particles (nanoparticles) are targeted by adding targeting groups onto their surface. These groups are capable of binding onto the receptors or tumor-specific antigen allowing for the molecule to release the drug product.

 

* the target group is designed in a manner that only allows the molecule to bind/attach onto the receptors or tumor-specific antigen. This means that the molecule can only get attached to the tumor cells, which is what is meant by targeting. Here, the type of target group on the molecule surface is dependent on the type of cancer cells.

 

Although the nanoparticles (nanocontainers) have been designed in a manner that allows the drug compound to remain intact until the molecule reaches the target cells, they are also sensitive to the internal environment of the cancerous cells. As a result, they are destroyed once they enter this environment, which causes the drug to be released. Once the drug compound is released, the treatment process begins.

As mentioned, the size of nanoparticles/carriers is very small, which is a big advantage. Because they are very small (similar to such molecules as receptors or enzymes) it's easy for these molecules to enter the cell where they can deliver the drug product. On the other hand, they can bind with surface receptors and interact with the biomolecules of the cell on the surface where they can also release the drug.

Depending on the intended purpose, scientists can easily modify these carriers to either interact with the surface on internal areas of the cell. This therefore gives scientists a lot of options when it comes to treating cancers.


Passive Targeting


Passive targeting is also referred to as passive tumor accumulation and benefits from enhanced permeability effects. As tumorous cells continue to grow, new blood vessels are formed in order to supply the new cells with nutrients and oxygen. However, these vessels are poorly formed and have large pores that make them leaky. As such, they allow large molecules to pass through.

On the other hand, these abnormal masses lack a normal lymphatic system, which makes clearance a problem. As a result, the tumorous cells retain the molecules that are allowed in. Because of these characteristics, nanoparticles that pass through into these masses are retained, which in turn allows for drug accumulation into these cells for enhanced treatment.

In passive tumor accumulation, such water soluble polymers as polyethylene glycol are added onto the surface of the nanocarrier to make the system last longer in the circulation system.




Active Targeting


Active tumor targeting is used to overcome the limitations of passive accumulation. Here, targeting serves to ensure the uptake of nanoparticles into the cells as well as intracellular comportments. This is made possible my adding a number of molecules on to the surface of the nanoparticle. These include:

 

  • Antibodies
  • Affibodies
  • Aptamers
  • Peptides


These additional molecules on the surface of the nanoparticles are essential in active targeting given that they enhance targeting where they serve to bind the receptors of the target cells.



Material Used for Making Nanoparticles


Nanoparticles used are made from a variety of materials depending on the needs or the researcher.

Some of the most common materials used to produce nanoparticles include:

 

  • Dendrimers  -Dendrimers are branched with three dimensional structures that make it possible to add more functional groups,
  • Liposomes - New polymer-coated liposomes are becoming more popular because of their durability. This makes them ideal in targeted delivery systems because they can last longer in the circulation system.
  • Metal - Various metal elements have been used to develop nanoparticles. A good example of this is iron oxide, which is used as an imaging agent.


*  the type of material used depends on the size of the nanoparticle required as well as the intended use



Current Research


While nanotherapy has been shown to present significant advantages in the treatment of cancer among a number of other diseases, research studies continue to be conducted in a bid to enhance its efficiency. Currently, a great deal of research is going towards multifunctionality of nanoparticles for nanotherapy.

Researchers agree that multifunctionality of nanoparticles would make them ideal in nanotherapy given that they would be able to not only carry more drug compound, but also have the following advantages:

 

  • Avoid being destroyed by macrophages
  • Efficiently permeate biological barriers
  • Selectively target the desired subcellular objects,
  • Deliver its components in a controlled way once it gets to the target cells/tissue

 

To achieve this, most studies focus on making modifications on the surface of the nanoparticles by adding various groups such as alkyl chains to add to the functionality of the particles; In doing so, it will not only be possible to enhance delivery, but also have better control of the system.

Research is also being directed towards completely eliminating the side-effects of nanotherapy. While it has been shown that the carriers can be used to target specific cells, this is yet to be achieved with the bioactive agents.

Given that the bioactive agents are unable to solely target cancerous cells, they end up affecting some of the nearby healthy cells where they cause irreparable effects. Therefore, research is also being geared towards associating the bioactive components with the target-specific nanocarrier system.

In 2015, researchers successfully developed a nanoparticle-based therapy (nanotherapy) that could treat multiple myeloma in mice. From the results, researchers were positive that this form of therapy can be used to treat cancer of the immune cells in the bone marrow in human beings.

In their study, the researchers found out that while this method of delivery presents a significant advantage in treating cancers, there is a need to improve on targeting, protecting the bioactive compound (drug product) and enhance delivery.

Using nanotherapy, researchers hope to block Myc, which has been found to be active in most cancers. However, Myc inhibitors have been shown to be highly potent, which means that they are highly reactive. As a result, there is a great need to improve the nanotherapy technology in order to ensure that the inhibitor is efficiently transported to the target cells without undergoing degradation. Given that the inhibitor has been shown to be very effective in animals, only an effective vehicle is required in humans to ensure the same efficiency.

Apart from the treatment of cancer, research is also being directed towards the treatment of a number of other disease including heart diseases and ischemia. For instance, researchers have been working with nanoparticles loaded with a hepatocyte growth factor protein (1K1) in therapeutic angiogenesis. This is seen as one of the ways through which researchers can grow new blood vessels in a bid to improve the supply of blood to some organs/tissues that do not receive sufficient amounts.

Studies have shown that this treatment method has the potential to help patients with the disease and aims to start new trials using another protein (1K1-NP) that has been shown to be better in the production of new blood cells compared to 1K1.

Other studies have shown that nanotherapy has the potential to help prevent repeated heart attacks among patients. Researchers used a high-density lipoprotein nanoparticle that was loaded with a statin drug in mice and discovered that the treatment helped target and lower inflammations in blood vessels. In human beings, this treatment method is expected to help patients by preventing new heart attacks by controlling inflammation in the arteries.


Nanotherapy Advantages


Although nanoparticles are very small, they have a larger surface area, which presents a significant advantage in drug delivery.

Having a large surface is a big advantage as it allows an opportunity for scientists to continually modify the molecules the way they want for different purposes. As such, it allows for increased functionalities of the molecules (nanoparticles).

In addition to a large surface area, the molecules can be controlled with regards to how they release the drug product. This, in addition to their stability prevents any wastage of the drug product given that sufficient amounts are delivered to the target cells.

As previously mentioned, one of the biggest issues with conventional chemotherapy methods is that the drug undergoes some changes before reaching the target cells or tissue. As a result of degradation, some amount of the drug is wasted. However, with nanotherapy, this is avoided due to the molecules transporting the drug component intact to the target cells/tissue.

In cancer treatment, this has been shown to be particularly beneficial when expensive bioactive materials are being used. This helps improve efficiency as well as cost-effectiveness of the treatment.

 

Drug solubility - Since most drugs tend to be hydrophobic, they are poorly dispersed in aqueous based biological solutions. As a result, some of the drug is not absorbed in to the vascular system, which means that some of the drug does not arrive at the target cells/tissue.

With nanotherapy, this problem is highly minimized as the surface of the nanoparticle can be modified in a manner that enhances solubility by adding hydrophilic groups. This helps improve treatment.

Specificity - Nanotherapy enhances specificity of drug delivery by increasing the concentration of the drug compound at the target site while reducing damage to healthy cells/tissues.




Challenges


Although nanotherapy presents many advantages in the treatment of diseases like cancer, it faces a number of challenges that are yet to be overcome.

The body's defense system is one of the challenges faced in nanotherapy. As is the case with other foreign substances (bacteria, foreign proteins etc) nanoparticles are identified as foreign and cleared by the body. This has been shown to reduce the efficiency of nanotherapy. For this reason, researchers are working to develop long lasting drugs or control nanocarriers so that they avoid certain routes in the body.

The surface area of nanoparticles in nanotherapy has also been shown to be a problem. While it presents a big advantage in that more functional groups can be added, this is also a problem given that the surface area results in high surface energy, which encourages binding of other proteins.

Some of the proteins that bind the surface have been shown to signal MPS macrophages, which in turn engulfs the nanoparticles. While these issues prevent nanotherapy from being the ideal form of therapy, research studies are being conducted to overcome these challenges.


Nanobots - With future applications in medicine and industry, scientists envision the manufacture of a functional nanite in approximately 25 years. Read on!

Carbon Nanotubes - While carbon nanotubes are complex structures, one can easily come to understand them and their many functions when broken down into individual components. Lets look at properties, modifications and their use in Atomic Force Microscopy. 

Microscopy in Biotechnology - Biotechnology is advanced and made more profitable through the extensive use of microscopy. Improvements in microscopy techniques will provide the necessary springboard for scientists to improve product functionality. 

Nanotechnology Products - In medicine, sports, transportation and environment.


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References


Gerhard Roedel, Hans-J├╝rgen Weiss, Michael Mertig, and Wolfgang Pompe (2013) Bio-Nanomaterials: Designing Materials Inspired by Nature.

Joseph W. Nichols and You Han Bae (2013)  Nanotechnology for Cancer Treatment: Possibilities and Limitations.

https://siteman.wustl.edu/nanotherapy-effective-in-mice-with-multiple-myeloma/

https://www.cancer.gov/sites/ocnr/cancer-nanotechnology/benefits

https://www.nature.com/articles/ncomms11221


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