Session C4
Paper # 115
Disclaimer—This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University
of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly
available information and may not provide complete analyses of all relevant data. If this paper is used for any purpose other
than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University
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GOLD NANOPARTICLES: A POSSIBLE CURE FOR PANCREATIC
CANCER
Julia McKay, [email protected], Mena, 1:00, Madeleine Braun, [email protected],Sanchez, 5:00, Erin Cannon
[email protected], Budny, 10:00
Abstract- Pancreatic cancer is particularly problematic
across the world due to its high resistance to chemotherapy
and radiation and the late stage in which the cancer is often
diagnosed. By the time that many people discover they have
the disease it is often too late for surgical intervention.
Gold nanoparticles (AuNPs) could be a potential solution
to this dilemma. AuNPs are a form of targeted drug
delivery that transport drugs to the main tumor and
metastasis site. AuNPs have properties such as
microscopic size, biocompatibility, and high surface
reactivity that allow them to effectively inhibit tumor cell
reproduction and growth. This technology is projected to
improve drug reception efficiency while providing a less
invasive treatment as compared to those currently
available. While this technology is theorized to have
several positive effects on those who face pancreatic
cancer, there are also some challenges with the
development of these AuNPs. As with any new technology,
there are several obstacles that those leading the
development are facing. This includes, the elimination of
long term cytotoxicity within the cell that may be caused by
the use of gold nanoparticles. Possible solutions to these
challenges are being investigated with the help of animal
and clinical experiments. The goal of these experiments is
to create a sustainable treatment option that could improve
the quality of life for those with pancreatic cancer.
Key Words- AuNPs, gold nanoparticles, nanotechnology,
pancreatic cancer, targeted drug delivery, therapeutic
devices
NANOPARTICLES: POSSIBLY
REVOLUTIONIZING CANCER
TREATMENT
Pancreatic cancer is the fourth leading cause of cancer
deaths in America. “It continues to have a survival rate of
less than five percent over five years, with a median
survival of only six months” [1]. Pancreatic cancer is an
aggressive and elusive disease that is typically diagnosed
in the later stages when it is too late for surgical
intervention to remove the tumor [1]. This disease is often
University of Pittsburgh Swanson School of Engineering 1
03.31.2017
viewed as incurable and, for that reason many scientists have
chosen to direct their efforts towards finding a new treatment
method. Scientists and engineers are exploring different forms
of targeted drug delivery as possible remedies. One that has
much promise is gold nanoparticles (AuNPs). They have several
advantageous properties that allow them to function well within
the body without causing harm. Researchers hope that when gold
nanoparticle development is complete, their implications will
improve the quality of life for thousands of people across the
globe.
WHAT IS TARGETED DRUG DELIVERY?
Targeted drug delivery is a method of transporting
medication to a patient in a manner that increases the
concentration of the substance in some parts of the body while
limiting it in others. This allows for healthy cells to remain
unaffected by the medication. The development of targeted drug
delivery systems is a sustainable approach in both chemical and
biological engineering to transporting drugs throughout the
body. In this context sustainability is the consideration of the
whole system, in which the process of drug delivery will take
place rather than just focusing on the process itself. The main
vector for delivering these drugs are forms of biological
nanotechnology, including nanoparticles. These nanoparticles
are being designed to combat the significant side effects of
traditional drug delivery methods. Targeted drug delivery
systems have proven, through in vitro and in vivo trials, to
function effectively within the human body. The developers of
these currently researched drug delivery systems have taken
many factors into account that simulate the human body such as
fluctuating pH, temperature, and other chemical interactions.
The nanodrug delivery systems are very integrated and
therefore require many different specialists. For example,
biologists, chemists, and engineers all work together to make the
best quality system possible. Dr. David A. Giljohann, an adjunct
professor of chemical and biological engineering at
Northwestern University, participates in research related to
controlled drug release systems. In his professional paper on
gold nanoparticles for medical applications he explained, “when
implementing a targeted release system, the following design
criteria for the system must be taken into account: the drug
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properties, side-effects of the drugs, the route taken for the
delivery of the drug, the targeted site, and the disease” [2].
The main method for transporting the drug delivery agent
into the body is oral ingestion. Once it is absorbed it can
enter the circulatory system and travel to its destination.
After the drug has reached its specified target the system
has completed its task. The primary goal of targeted drug
delivery is to improve the efficacy of drug delivery while
reducing the side effects. The advanced drug delivery
systems currently being developed could potentially meet
both of these goals.
patients who do have surgery, because it comes back about 85
percent of the time. At best, 25 to 30 percent of patients are alive
five years after surgery” [4]. These statistics are a harsh reality
for those who battle pancreatic cancer, regardless of when they
were diagnosed.
APPLICATION AND IMPACTS
RELATING TO PANCREATIC CANCER
Cancer cells replicate at a faster rate than normal cells
and divide to form a cluster known as a tumor. Once this
tumor has formed it is difficult to remove because it has
already intertwined with vessels and other organs. Tumors
caused by pancreatic cancer are especially risky because
they easily metastasize, meaning that the cancer cells can
spread to any part of the body through the lymph nodes and
begin to grow there. Eventually this leads to the cancer
taking over the entire body and the need for drastic
treatment measures [2].
Currently, pancreatic cancer is considered by many to
be an “incurable” disease. The difficulty in treatment of
pancreatic cancer is caused by a variety of factors. The
symptoms of this disease occur much later than other forms
of cancer and often depend on the initial location of the
cancerous cells within the pancreas. Unless a patient has a
family history of pancreatic cancer, due to its hereditary
nature, it is unlikely that they will be tested for the disease
without the presence of symptoms. Testing is not done on
the general public because there are limited options for a
non-invasive or cost effective test that can easily be done
prior to the appearance of symptoms [3]. A lack of testing
allows for the tumor to spread across the body and becomes
so invasive that attempted removal of the tumor is rarely
possible or effective.
The only current method to fully eradicate pancreatic
cancer cells from the body is complete surgical resection.
Due to the positioning of the pancreas in the body, it is a
very difficult organ to surgically access [3]. The location
of the pancreas can be seen in Figure 1. Also, in order for
the tumor metastasis site to be removed, surgeons must
remove large portions of the pancreas, sometimes up to
95%. This greatly affects the health of the patient. While it
is possible to live with only a small portion of the pancreas,
it requires large lifestyle changes such as daily insulin
injections and frequent hospital visits. Doctors must
continuously monitor hormone levels and residual cell
growth to ensure that the cancer does not return. According
to Dr. Allyson Ocean, a respected oncologist at the Weil
Cornell Medical Center, “the prognosis is poor even in
2
FIGURE 1 [5]
Anatomical diagram of the human body
(pancreas in red)
Although surgical resection is the only potential “cure” for
pancreatic cancer, there are many treatment methods currently
in existence. Two of the most common therapeutic treatments
are chemotherapy and radiation. However, these solutions tend
to be relatively unsuccessful. The pancreas has one main blood
supply, known as the greater pancreatic artery, through which
chemical substances can travel to the pancreas. Thus, the
probability of chemical injections into the bloodstream
impacting the tumor is very low. During the process of
chemotherapy or radiation treatment, a significant number of
healthy cells are killed, due to the lack of specialized targeting
agents. The molecules cannot efficiently locate the cancer cells
and, as a result, end up killing a large number of healthy cells
[3]. Considering that the three main treatment options for other
cancers are not sustainable for pancreatic cancer, and have major
side effects, many have sought an alternative method to treating
this disease. The most promising solution comes from targeted
drug delivery systems.
For those with pancreatic cancer, nanotechnology provides a
potential cure that has been previously unavailable. These
patients often have to go through the painful and strenuous
process and recovery of chemotherapy and radiation. Based on
the potential impacts of this technology, scientists have chosen
to further explore targeted drug delivery. The application of
targeted drug for pancreatic cancer could potentially provide a
better quality of life and survival rate than currently offered, thus
theoretically providing a more sustainable option.
Madeleine Braun
Erin Cannon
Julia McKay
EXPLANATION OF GOLD
NANOPARTICLES
The research behind nanoparticles stems from the
naturally existing organic transportation agents within the
body. These include proteins, liposomes, and
polysaccharides. By observing functions of the compound,
modern forms of nanotechnology have been developed to
mirror the capabilities of these organic agents. Gold
nanoparticles (AuNPs) are among the most studied and
promising of nanotechnology. Successful animal testing
and in vitro experiments on human cells have already taken
place [2]. Because of the biocompatibility of these
nanoparticles many exciting applications are foreseen. The
foremost of these applications is in targeted drug delivery.
Why Gold?
In the days of the ancient Egyptians, it was believed that
ingesting gold had medicinal properties. Many applications
of gold have since been discovered and are currently being
researched. Interest in this specific element, gold, is due to
its biocompatibility and ideal properties. These properties
include, being non-toxic, easily shaped, and never
corroding or tarnishing. Gold is a good conductor of both
heat and electricity. This is advantageous when it comes to
dealing with the natural electric signals within the body.
The surface chemistry of elemental gold is highly reactive
with other substances [2]. This allows for more versatility
in the design of the nanoparticles and what they can deliver.
Unique Characteristics of Gold Nanoparticles
Gold nanoparticles have a variety of beneficial
characteristics that allow them to perform efficiently
within the body. The properties of elemental gold and the
structure of the nanoparticle itself enable them to act as
multimodal drug carriers [3]. This means that they can be
used not only to transport the medication, but also to image
the disease internally, sensitize cells and potentially apply
electromagnetic radiation to disease sites. These
characterics allow for AuNPs to act as transporters of
substances, when on their own in the body, prove to have
poor cellular penetration, solubility, and pharmacokinetics,
properties that relate to how pharmaceuticals move
throughout the bloodstream to specific tissues and organs.
“AuNPs are one hundred times smaller than human
cells and can offer unprecedented interactions” [6]. Their
size allows them to enter into the cell through the plasma
membrane. The most commonly used nanoparticle is the
nanosphere [7]. Nanospheres have a large surface area
where ligands can be attached and interactions can occur
[1]. This increases the likelihood that the nanoparticle will
make it to the disease site and be accepted by the cell.
Typically, foreign substances are rejected by the body.
Therefore, scientists have been making alterations to the surface
of nanoparticles that make them compatible with cancerous
tissue to ensure that gold nanoparticles can overcome this
obstacle.
Metallic nanoparticles are conductors which means that they
have electrons scattered throughout the particle which tend to
rest on the surface, but are free to move throughout the particle.
It is this trait of AuNPs that allows them to not only be drug
deliverers, but act as multimodal agents. Imaging of the cancer
is crucial in predicting what treatment options are best suited for
each patient's case, and dosage amounts to be delivered.
Drug Carriers to Tumor Sites
Gold nanoparticles as a form of targeted drug delivery
perform the intended equivalent task as that of chemotherapy
and radiation. The AuNPs transfer the same anti-cancer drugs as
those currently used in chemotherapy such as emcitabine,
carmustine, paclitaxel and doxorubicin to limit tumor growth,
but they do it in a more direct and efficient manner [8]. This
minimizes side effects and long term damage to regions of the
body.
The most important characteristic of the gold nanoparticle is
its malleable design. There are multiple options for the shape of
the nanoparticle, each with a different purpose. Overall, their
structures have universal features. These include a center, where
the gold is contained and surrounded by a compact protective
layer. This is known as the Stern Layer. This is covered with a
second biocompatible layer known as the Gouy layer. The Gouy
layer is where the drug is attached using ligands. Ligands are
molecules that are attached to a metal ion using coordinate
bonding [1]. This bonding can either be covalent or noncovalent. Often it occurs between a functional group and a
ligand. This functional group is the drug that the nanoparticle is
delivering. The structure of the gold nanoparticle is shown in
Figure 2. The functional group keeps the ligand attached to the
surface of the nanoparticle. The body now recognizes the
nanoparticle and permits delivery of the drug.
FIGURE 2 [6]
The complex structure of the Gold Nanoparticles with
ligands, R-Group, and drug attached to the surface
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Multiple factors can influence the performance of these
ligands. Binding affinity of the targeting ligand is crucial
for favorable interactions between the surface and the
ligands. Binding affinity is the strength of the attractions
between the ligand and the surface of the nanoparticle. If
the ligand has a strong affinity, then it will be more likely
to bond and aid in the drug delivery process. If there is low
affinity of a ligand to its receptor, this limits targeting
efficiency.
Another component that impacts the construction of this
structure is the surface density of the ligands. The more
densely packed the ligands are on the surface, the more
they can penetrate the cancerous tissue. The nanoparticles
will then be more effective in destroying the malignant
cells. This activity is dependent upon the nanoparticles
being delivered as one unit to the metastasis site. Targeted
ligands need a long half-life to provide sufficient time for
the drug to reach the target at therapeutic levels.
After all of the previous constraints are met pertaining to
the structure of the ligand and the characteristics of the gold
nanoparticle, the nanoparticle can finally reach its
destination. Once there, the gold nanoparticle enters the
cell through receptor-mediated endocytosis. This means
that a small hole opens up in the plasma membrane and
allows the particle to enter. It then closes up behind it so
that nothing from inside of the cell can escape. The particle
is now inside of the cancerous cell where it can finally
perform its task, releasing the drug. The coating on the
outer surface of the nanoparticle is able to partition
hydrophobic molecules from surrounding aqueous medium
[6]. This tells the nanoparticle the correct time to release
the drug, which in when it is either inside of the cell or just
outside of it, depending on the delivery system. Once
released, the drug travels throughout the cell and triggers
apoptosis. This means that the cancer cell dies and the
nanoparticle has completed its task [9].
Enhanced Permeability and Retention
In order for gold nanoparticles to effectively reach the
site of the malignant cells, the properties of such cells must
be studied in order to better understand nanoparticle-cell
interactions. Due to the abnormally large presence of blood
vessels within tumor cell clusters, the increased
permeability of these blood vessels, made possible by
loosely compacted vasculature, and lack of lymphatic
drainage, nanoparticles are able to invade and accumulate
in the tumor tissue [8]. This is known as the Enhanced
Permeability and Retention (EPR) Effect, which was first
established by Matsumura and Maeda. Although these
qualities, caused by EPR, generally improve delivery of
chemotherapeutic agents to cells through nanoparticles, it
only results in a maximum ten-fold increase in delivery in
comparison to unaffected organs. This small increase is
insufficient for achieving optimal therapeutic levels in
patients suffering with cancer [8, 9]. This led scientists to
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utilize these traits of tumor tissue to passively target cancerous
tissue in addition to other modifications on the nanoparticles
themselves for active targeting to improve the levels of drug
successfully delivered to the cancerous cells.
The Importance of Surface Receptor Targeting
It is impossible for any type of nanoparticle to be able to track
and locate a specific area of the body without chemical
modification to the surface of the particle. There are two distinct
types of drug targeting systems that are used: active and passive.
Active targeting involves the conjugation of natural biological
agents which track and treat disease such as antibodies and
peptides. Passive targeting is achieved by taking advantage of
the EPR effect previously discussed. Both methods can be used
within a single nanoparticle to improve both the accuracy and
precision of the targeting [10].
It is well known that within most cancerous cells the
epidermal growth factor receptor (EGFR) is often overexpressed
by the EGFR gene. This factor is overexpressed in up to 90
percent of pancreatic cancer cells, and this expression has been
a huge focus of a variety of different targeting treatments for
pancreatic cancer. These researched treatments include a drug
called Erlotinib, a drug currently listed as an available potential
treatment by the American Cancer Society for pancreatic cancer,
which is currently used in addition to chemotherapy and
radiation. The EGFR gene mutation allows for cancer cells to
constantly grow and divide into clusters of tumors. By targeting
cells with this mutation-using surface-modification, drug
delivery could be possible. Studies have been performed using
AuNPs conjugated with anti-EGFR proteins, which were
effective in tracking cells with the overexpressed EGFR on the
cancer cells surface when compared to similar testing on healthy
cells. Another method to targeting this specific gene through
surface modification is the conjugation of whole antibodies or
fragments of one to utilize natural targeting abilities of the body
[11]. This method grew in popularity due to recent FDA
approval of antibody immunotherapies in other fields of study.
In recent research, there has been promising statistics using this
antibody approach on cancerous tissue. Alyssa Master, a
researcher of biomaterials and drug delivery systems at Case
Western Reserve University, referenced, “several studies
including those performed by El-Sayed et al. and Melancon et
al. have shown the ability to cause almost 100% cell death in
vitro through the use of these antibody-targeted gold
nanoparticle systems” [10]. Based on these results, this is clearly
a favorable surface modification method. However, it is
extremely expensive to use and experiment with living
antibodies.
Peptide conjugation is a common and promising new area of
research within drug delivery that can be used to locate the
cancer using this gene mutation as well to deliver
chemotherapeutics to diseased cells. A peptide is a compound
consisting of two or more amino acids linked together in a chain.
One EGFR-specific peptide currently being researched is called
“GE11”. The results on several in vitro human cell lines showed
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that the GE11 peptide targeting method increased cellular
uptake of the drug, and resulted in 80% cell death in cancer
cells with the gene mutation [10]. Cellular uptake, the
process of absorbing a substance into a cell, is a key
component to a successful drug delivery system [8].
Electromagnetic Properties Resulting in Imaging,
Detection, and Thermal Therapy
Receptor-Mediated Endocytosis
Receptor-mediated endocytosis is the final step of drug
delivery for AuNPs, in which the subcellular nanoparticles
enter the cancerous cell itself to release the drug. Attaching
specialized ligands can allow for the nanoparticle to
penetrate cancerous cells themselves and release the drug
within the cell resulting in apoptosis, or cell death. The
ligands used to modify the surface of the cell must be
compatible with cellular surface receptors of the cancerous
cells. If the particles successfully bind with the receptors,
then the nanoparticle can be internalized into the cancerous
cell through a process called receptor-mediated
endocytosis which is typically used by healthy cells to
intake metabolites, hormones, and other proteins [7]. This
process can be seen in Figure 3.
Although not the primary function this paper focuses on, an
important part of this technology is the imaging and detection of
cancer cells both prior to treatment and the residual cells left
after treatment. It is the electrons within the gold of these
particles that allow for this advantage. Gold utilizes its intense
light scattering power to identify cancerous growths prior to the
attempted resection of the affected area. This could allow for
surgeons to judge whether surgery is possible or if it will be
effective. They can also be used during surgery to help the
surgeon visualize the site on a cellular level. “Gold nanoparticles
with diameters between 12 and 20 nm are known to efficiently
scatter visible light in the wavelength region around 530 nm and
can thus easily be detected by wavelength selection using optical
methods such as dark field or confocal microscopy” [12]. This
means that gold particles of a certain size coupled with light of
a specific wavelength scatter the light in such a way as to
optimally visualize infected tissue. Examples of these imaging
processes can be seen in Figure 4. This discovery could indicate
ability for earlier detection and more targeted treatment in cancer
patients.
The process of imaging and detection consists of two distinct
sections, absorption and scattering. When metal nanoparticles
are exposed to light, the electrons circling the particle band
together. This gives the surface of the particle a negative charge.
Because of this, the particles oscillate at a precise frequency and
this is referred to as surface plasmon resonance (SPR) [7]. Then,
based on the SPR, the energy absorbed from the light by the gold
in the particles is then scattered hitting the targeted organic
material in the form of heat [8].
FIGURE 3[7]
Receptor-Mediated Endocytosis of gold nanoparticle
into cancerous tissue
The intake of nanoparticles largely depends on the size
of the particle. The optimal structure of nanoparticle for
this specific process is a spherical gold nanoparticle with a
diameter of 50 nanometers. These results proved to be
consistent regardless of the dosage and ligands used for
targeting Prior to entering the cells the drug-ligand-surface
bonds are stable, but within the cell due to the chemical
conditions of the cytoplasm, the jelly-like material within
the cell, these same bonds become unstable causing the
release of the drug from the nanoparticle. This allows for
the chemotherapeutic to interact with the cancerous cell
and eventually lead to the death of the cell [7, 11].
FIGURE 4 [13]
Example of imaging methods of in vivo rat testing
based on conductivity and heat transfer
In addition to the benefits of free electrons for imaging
purposes, their conductive properties of both electricity and heat,
allow them to trigger hyperthermia in an infected area.
Hyperthermia is a condition in which a system is a few degrees
above its ideal temperature. If a cell is raised three to six degrees
Celsius above its optimal temperature it can die or become
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extremely damaged. Metallic nanoparticles have the ability
to induce hyperthermia in clusters of cancer cells. If this
technique is carried out along with the delivery of the
chemotherapeutic, then the cell will be more susceptible to
death. This process is called photothermal therapy. “For
imaging, larger nanoparticles are preferred because of
higher scattering efficiency, whereas for photothermal
therapy, smaller nanoparticles are preferred as light is
mainly adsorbed by the particles and thus efficiently
converted to heat for cell and tissue destruction” [14].
Therefore, when used for drug delivery, smaller
nanoparticles are optimal.
CHALLENGES IN DEVELOPMENT OF
GOLD NANOPARTICLES
As with any new technology being developed, there are
many challenges that the engineers at the forefront of this
technology are facing. They must ensure that the
technology not only upholds the health standards set out by
the U.S Food and Drug Administration (FDA), but also are
ethically accepted and trusted by the community. The use
of gold nanoparticles as a form of pancreatic cancer
treatment has not yet been approved by the FDA. Scientists
are still perfecting the technology and ensuring its
reliability. Until it is officially accepted, it will not have a
set of specific guidelines put in place so that it can be used
on patients.
One of the main obstacles that engineers are facing with
the function of the product is making sure that it does not
aggregate within the body. Aggregation is when the
nanoparticles cluster together. This can be dangerous as it
can lead to blood flow blockages and cause ischemia,
insufficient blood supply to a specific region of the body.
One way that engineers are trying to prevent aggregation is
with the addition of a monolayer or bilayer cap to the gold
nanoparticle [6]. Although this technique has potential, it
has not proven to fully prevent aggregation. Researchers
are still working on perfecting the design and composition
of these caps.
The development and formation of gold nanoparticles
to optimize their efficiency targeting, imaging, and thermal
therapy has proven to be difficult. Although AuNPs are
capable of performing all three tasks, each of these is
dependent on the structure and size of the particle.
Nanoparticles greater than six to eight nanometers are not
efficiently excreted from the body, yet the most effective
particles in terms of cellular uptake would be fifty to sixty
nanometers in diameter due to their large surface area for
conjugation. Imaging nanoparticles tend to be most optimal
when they are larger whereas for thermal therapy ideally
they would need to be smaller. This inconsistency in best
possible size for each mode of the nanoparticle has limited
success of all three modes working together in testing [10].
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Research into Cytotoxicity for Sustainable Gold
Nanoparticles
A major challenge that has been a concern for all metallic
nanotechnology being researched is the possibility of
cytotoxicity due to long term exposure of cells to the metal.
Cytotoxicity is the ability of certain chemicals to harm or destroy
living cells. Cells are considered the basic unit of human life, so
any interference with their function is carefully studied. The
ideal size of nanoparticles based upon in vitro research is often
too large for the AuNP to exit cells once they enter and they often
cannot be excreted naturally, which would be preferred. This
means that that the majority of gold nanoparticles used for the
treatment would remain within the body for the duration of the
patient’s life after treatment [15].
Continued medical complications due to the cytotoxicity
from AuNPs could potentially lead to death or a poor quality of
life and would lead the AuNPs to be considered an unsustainable
treatment method. As of now there are long-term experiments
going on for metallic nanoparticles to ensure that this will not
pose this extreme of an effect. This research remains premature,
so no simple conclusions have been drawn as to whether gold
nanoparticles would be safe enough for a clinical setting. Based
on existing uses of gold in unrelated medical applications such
as the use of gold-based compounds for the treatment of
rheumatoid arthritis, gold usage has been safe and bulk gold is
considered biocompatible and “chemically inert” within the
body. In the application of gold in use of treatment for cancer,
nanoparticles will have to be compatible with a variety of
complex solutions such as the cytoplasm of cells and blood. The
continued nanoparticle-fluid reactions on a molecular level have
been the focus of cytotoxic research.
The concern of harmful side effects in a patient following
AuNP cancer treatment is similar to those of chemotherapy and
radiation. As discussed previously, the effects of chemotherapy
and radiation on a patient with pancreatic cancer tend to be very
harmful. There is a possibility that all cancer patients face when
receiving either of these treatments that they could die from the
effects even if it successfully kills the cancer. Therefore, the
treatment methods discussed in this paper could be considered
not fully sustainable and could be replaced by future alternatives.
Scientists and engineers are working to ensure that the
reactions between golf nanoparticles and the cell will not lead to
any impairment of the cells within the body. Other forms of
nanoparticles are also being researched to compare their
respective advantages and disadvantages to those of gold
nanoparticles
Comparison to Polymeric nanoparticles
Due to the rise in interest nanotechnology and projected
growth of it within the next few years, there has been research
on an assortment of different materials and structures of
nanoparticles as drug deliverers, not just gold. One of the most
common materials used to construct nanoparticles currently
being researched is polymers. Polymers are large complex
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molecules that can be found naturally or synthesized in a
laboratory. They are built out of many smaller often
repeating units that form very useful materials [16]. This
material is beneficial for pancreatic cancer treatment due to
their advantageous properties. Similar to gold
nanoparticles, polymeric nanoparticles can function
effectively within the human body without causing
significant harm.
Polymeric nanoparticles are of high interest in the field
of nanotechnology because they tend to be biodegradable,
biocompatible, cost-effective, and very versatile since they
can be constructed out of countless chemical formula units.
Polymeric nanoparticles can be surface functionalized
similarly to how gold nanoparticles are in order to target
drug delivery [16]. As of now they have been researched
more heavily than metallic nanoparticles, so there has been
more success in their testing.
Although polymers are shown to have some advantages
over AuNPs, they also have disadvantages that need to be
investigated. Some polymers, mostly natural hydrophilic
polymers, are hard to produce batch-to-batch because the
combination of formula units is so unique. Another
disadvantage is a result of polymers being naturally
formed, because of this it is possible for the body to form
antigens that will label the nanoparticle as an invader and
destroy the particle prior to it reaching its destination. In
addition, polymeric nanoparticles are often faulty if not
operating in optimal conditions. For example, if the pH is
imbalanced or the temperature is too low or high, the
particle could release its drug prematurely or not at all [16].
Another disadvantage when compared specifically to
AuNPs is that they only currently act as drug carriers and
are not considered to be multimodal. Because of this
specification, polymeric nanoparticles can perform fewer
functions within the body as compared to gold
nanoparticles. While this may not seem to be a good thing,
this means that more of the research into polymeric
nanoparticles goes into their application to cancer
treatment, while gold nanoparticles research branches off
into multiple categories as explained previously.
ETHICS OF GOLD NANOPARTICLE
RESEARCH AND DEVELOPMENT
In addition to technological barriers to the formation of
gold nanoparticles, engineers working with AuNPs are
facing ethical and economic issues. The development of
new medical technology is a long and difficult process,
consisting of product formulation, lab testing, animal
testing, and clinical trials. Following all of these steps, the
product still may not be ready for human use. Even if the
technology performs perfectly in every stage of its
development, and does not need any modifications, the
process can still take up to ten years [17]. Once the product
is available to the public, it takes time for people to begin
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to trust it. Until there are human tested statistics, beyond clinical
trials, to support the claims of the product, it will not become a
standard treatment. Especially for a disease as widespread as
cancer, it would most likely take even longer for a new cancer
treatment to circulate into use, because it would be met with
skepticism.
Those who are developing this cancer treatment face a
struggle between fast tracking the process of development while
possibly not being as thorough as they should be or waiting to
release the treatment as thousands of people die from the disease.
World Pancreatic Cancer Day, an organization that spreads
awareness of pancreatic cancer, stated that “an estimated 985
people worldwide die from pancreatic cancer every day” [18].
This statistic demonstrates the need for prompt and effective
advancements in pancreatic cancer treatment. With this being
said, there are multiple consequences that would come from
releasing a product before it is truly prepared. If the product has
a problem, it could end up doing more harm than good. This
would create a stigma associated with the treatment method and
would limit its future application.
How Cost Influences Research
After the treatment method is developed and introduced into
industry, there is still the over lining issue of making the product
affordable for the masses. A huge misconception of this new
technology is that, because gold is involved and is seen as an
expensive material the production of AuNPs will be incredibly
expensive. This has proven to be untrue based on the synthesis
of the nanoparticles used recently in the trials we discussed.
When produced in large quantities the total cost of gold salt
required to produce a “full-course phase I dosage” of
nanoparticles was 12 cents [7]. When it comes to the expenses
of the nanoparticles, the issue is not with the synthesis of the
product itself, but rather with the research and potentially longterm clinical trials behind still required prior to its appearance in
industry. Potentially, billions of dollars are put into researching
new medical technology. The companies designing the product
will expect a return on their investment, therefore when the
product is released it will be expensive. As a result, many of the
people who need the treatment will not be able to afford it which
would lead to it being considered economically unsustainable.
This creates an additional dilemma for those researching the
technology.
THE OUTCOME OF GOLD
NANOPARTICLES ON CURRENT
PANCREATIC CANCER TREATMENTS
Pancreatic cancer affects the lives of thousands of people
across the globe. Therefore, alternative treatment methods for
pancreatic cancer have become a recurring research topic in the
field of medicine as well as in engineering. This technology
provides a potential solution over current forms of treatment,
such as chemotherapy and radiation. It has the capacity to be
Madeleine Braun
Erin Cannon
Julia McKay
both effective in its eradication of cancer cells and in its
protection of unaffected areas. The advantageous
properties of nanotechnology-based treatments allow for
them to supply both a protective and healing function
within the body. These properties include biocompatibility,
high surface-to-mass ratio, enhanced permeation of
cancerous tissue, and improved selectivity over current
treatment. Gold nanoparticles could not only become a way
of allowing for a less painful treatment process for cancer
patients, but also provide hope for a cure in the near future.
There is still a long way to go before this technology is
approved for human use. It is currently only being tested
on animals and on in vitro cell lines. Although there has
been significant success in these stages, it is unpredictable
whether this will translate in human clinical trials. The
human body often reacts differently to drug treatments than
animals and therefore, the potential of the product will not
be confirmed until the final stages of testing. Overall, gold
nanoparticles as a form of targeted drug delivery for
pancreatic cancer treatment could possibly revolutionize
the way society views cancer. It is currently viewed by
many as an incurable disease, but with the establishment of
this new technology, it may limit its threat on society.
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b3ea030903e53a2
ACKNOWLEDGMENTS
We would like to thank our professors for helping us to
become better students. We would also like to thank our
parents for supporting us and allowing us to pursue our
goals. Finally, we would like to acknowledge all of the
resources here at The University of Pittsburgh that we have
utilized while writing this paper. They include the Writing
Center, the Engineering writing instructors, the library
staff, and our co-chair. Thank you for guiding us through
this process.
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