Nanoparticles, Research, Advantages and Challenges
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
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
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.
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 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
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 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:
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
- 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
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
- Avoid being destroyed by macrophages
- Efficiently permeate
- 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
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
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.
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.
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
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
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
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.
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.
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Gerhard Roedel, Hans-Jürgen
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.