Session B4
176
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GRAPHENE AND ITS APPLICATION AS A DRUG DELIVERY SYSTEM
Taylor Daniels, [email protected], Mahboobin 4:00, Jessica Sorick, [email protected], Mena Lora 1:00
Abstract — Graphene is a carbon allotrope that is an
extremely versatile material, and its unique properties have
been found useful in the area of targeted drug delivery,
specifically for cancer therapy. Graphene is the lightest and
strongest material and can conduct heat and electricity better
than any material on Earth. These are some of the properties
that give graphene the ability to transport anti-cancer drugs
to the distinct part of a cancer cell where they will be most
effective. Graphene-based drug delivery systems have been
found to be responsive to many internal and external physical
stimuli typical for effective drug delivery systems, such as pH,
redox potential, biomolecules, light, magnetic field, and
temperature.
Cancer is one of the greatest health care problems
facing society today. The current chemotherapy methods
being used to treat cancer have extreme side effects and varied
responses between patients. In studies at the University of
Manchester and University of Calabria, graphene oxide could
target and neutralize cancer cells, thus preventing the
recurrence of tumors. Graphene does this by entering the
cancerous tumors through nearby blood vessels that leak due
to the tumor. The graphene oxide causes the cancer stem cells
to become completely non-cancerous. Therefore, the cells no
longer can create tumors. Thus, graphene’s success as a drugdelivery system will be thoroughly investigated and explained.
across an array of fields including membranes, composites and
coatings, energy, biomedical applications, sensors, electronics
and other nanotechnologies. New uses for graphene are being
discovered so rapidly that a concise list such as this cannot
begin to explain the diversity of graphene.
One specific area of interest in graphene for the
biomedical field is in its potential as a drug delivery vehicle.
In a scholarly article on graphene’s drug delivery applications,
it is stated that graphene is biocompatible and responsive to
many stimuli vital for effective drug delivery [2]. Due to its
biocompatibility and unique properties, research is being done
on graphene’s ability to carry anticancer drugs. The future
looks bright for graphene in the drug delivery field,
specifically with anticancer related drugs.
Graphene’s use in each of these areas is important and
useful for society in everyday life. Many of graphene’s
applications are sustainable by either reducing waste or by
improving quality of life. Recent breakthroughs in graphene’s
ability to effectively transport anticancer drugs could be the
next step in finding a cure for cancer. What is known today
about graphene and all of its possibilities would not be
possible without the research and studies that began about
seventy years ago on graphene and its existence.
Key Words — Cancer treatment, drug delivery, graphene,
graphene oxide, nano-carriers
Although graphene was not isolated until 2004, studies
began around 1947. Graphene was known to be millions of
extremely thin layers stacked together to form graphite, such
as in a pencil. According to the University of Manchester, the
fact “that electric current would be carried by effectively
massless charge carriers in graphene was pointed out
theoretically in 1984, and the name 'graphene' was first
mentioned in 1987 to describe the graphite layers that had
various compounds inserted between them. The term was used
extensively in work on carbon nanotubes, which are rolled up
graphene sheets” [3]. Many of the theoretical explanations and
descriptions of graphene from over fifty years of studies were
found to be true in 2004 by two professionals at the University
of Manchester.
Graphene was discovered relatively recently in 2004 at
the University of Manchester by Prof Andre Geim and Prof
Kostya Novoselov. According to the University of
Manchester, “One Friday, the two scientists removed some
flakes from a lump of bulk graphite with sticky tape. They
GRAPHENE IN THE WORLD TODAY
Graphene: A Carbon Allotrope
Graphene is a material that has been turning heads in
recent news because of its great number of useful properties
and uses in various areas. Graphene is a versatile carbon
allotrope that is the lightest, thinnest and also strongest
material known on Earth. Due to graphene’s versatility,
according to La Fuente, CEO of Graphenea, “Initially this will
mean that graphene is used to help improve the performance
and efficiency of current materials and substances, but in the
future, it will also be developed in conjunction with other twodimensional (2D) crystals to create some even more amazing
compounds to suit an even wider range of applications” [1].
The possibilities for graphene are endless, and its uses span
University of Pittsburgh, Swanson School of Engineering 1
Submission Date 3.31.2017
The History and Development of Graphene
Taylor Daniels
Jessica Sorick
noticed some flakes were thinner than others. By separating
the graphite fragments repeatedly, they managed to create
flakes which were just one atom thick. They had isolated
graphene for the first time” [3]. They were both awarded the
2010 Nobel Prize in physics for their groundbreaking work in
isolating graphene. Geim and Novoselov sparked a huge
interest in graphene that has scientists across the world
researching graphene’s amazing properties and capabilities.
Although Geim and Novoselov isolated graphene with a
simple method of sticky tape and a lump of graphite, graphene
today is synthesized in many different ways, including
bottom-up synthetic approaches such as chemical vapor
deposition, arc discharge and epitaxial growth. The most
common method used is a top-down approach using
mechanical, physical and chemical exfoliation of graphite
with strong acids and oxidants. These methods require
extensive oxidation of aromatic structures in order to weaken
the Van der Waals interaction between graphene sheets
followed by their exfoliation and dispersion in solution [2].
Research is being done to optimize the synthesis of graphene
and graphene oxide to make the process greener, less wasteful,
more cost effective, and overall more sustainable.
undergoing tension or compression in one direction. It is
mathematically calculated by longitudinal stress divided by
strain. Therefore, because graphene has a high Young’s
Modulus, it is elastic. Fracture strength is the pulling stress
required to break a material. Therefore, with a high fracture
strength, graphene is strong and difficult to break. Graphene’s
high elasticity and fracture strength, along with its many other
properties are useful in many industries. Some industries
being substantially impacted by the combination of
graphene’s amazing properties include transport, medicine,
electronics, energy, defense and desalination.
Graphene has many specific electrical properties,
including great conductivity. Graphene offers ballistic
transport, linear current-voltage (I-V) characteristics, and huge
sustainable currents (>108 A/cm2). Graphene transistors show
a rather modest on-off resistance ratio [5]. All of these
electrical properties of graphene are useful properties for
metallic transistor applications.
Another unique property of graphene is that “Its
electrons behave like particles of light, the massless photons
that, in a vacuum, relentlessly move ahead at a speed of 300
million meters per second. Similarly, electrons travelling in
graphene behave as if they did not have any mass and move
ahead at a constant speed of one million meters per second.
This opens up the possibility of studying certain phenomena
more easily on a smaller scale, i.e. without the use of a large
particle accelerator. Graphene also allows scientists to test for
some of the more ghost-like quantum effects that so far only
have been discussed theoretically” [6]. This is such a unique
property that will be extremely useful for scientists. The fact
that graphene can help study certain phenomena that before
could only be studied using a particle accelerator, or never at
all, is outstanding.
Graphene oxide, shown in Figure 2, a derivative of
graphene, has been found to be useful in many applications
and also have some interesting and useful properties.
According to Johnson of IEEE Spectrum, a scientific
magazine, “When graphene oxide is exposed to a certain pH
level it transforms into liquid crystal droplets. Previously,
researchers needed atomizers and other mechanical equipment
to change graphene into a spherical form” [7]. Changing
graphene into liquid crystals is not only simple, but also
inexpensive. This special property, along with graphene not
having any magnetic properties, can be something useful in
many applications, primarily in drug delivery.
The Properties of Graphene
Graphene, the world’s first two-dimensional material, is
the strongest material on Earth; it is 200 times stronger than
steel. It is this strong while still being extremely flexible and
ultra-thin. Graphene is also a great conductor, perfect barrier
and completely transparent. Graphene is a perfect barrier
because it is impermeable to all gases and moistures.
According to the University of Manchester, graphene is a
hexagonal lattice of carbon atoms in a honeycomb like
structure [3]. This lattice structure, shown in Figure 1, is one
feature that makes many of graphene’s properties possible.
FIGURE 1 [5]
Structure of Graphene
In an article on graphene and graphene oxide as
nanocarriers, it is stated “Due to its unique structure and
geometry, graphene possesses remarkable physical–chemical
properties, including a high Young’s modulus, high fracture
strength, excellent electrical and thermal conductivity, fast
mobility of charge carriers, large specific surface area and
biocompatibility” [2]. Young’s modulus is a numerical
constant that describes the elastic properties of a solid
FIGURE 2 [5]
Structure of Graphene Oxide
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possibly roll up like a newspaper. According to the University
of Manchester, “Flexible, wearable electronics take advantage
of graphene's mechanical properties as well as its
conductivity. Indium-tin oxide is currently used for touch
screens as it conducts well but it is brittle” [3]. Graphene,
being almost completely transparent, would be a great
alternative for touch screens. With graphene being the
strongest material currently known on Earth, using graphene
instead of plastic or glass for touch screens would reduce an
enormous amount of waste because it would create an
ultimately indestructible smartphone. Smartphones are
damaged and broken regularly, but with graphene,
smartphones would become much more sustainable, lasting
much longer. Graphene’s use in touch screen products, like
smartphones and tablets could become extremely useful and
in demand in today’s technology filled world. The demand for
new technology is growing and something new such as
flexible smartphones would be an extremely successful
innovation.
Applications of Graphene
One example of graphene in the area of composites and
coatings is in aircrafts. It is expected that graphene will
eventually be used to replace steel in aircrafts, reducing weight
and increasing fuel efficiency and range while still being
strong. According to La Fuente, CEO of Graphenea, “Due to
its electrical conductivity, it could even be used to coat aircraft
surface material to prevent electrical damage resulting from
lightning strikes” [1]. Graphene’s ability to better aircrafts in
all of these ways could create a lighter, more economical,
stronger and safer aircraft, benefiting all of society since air
travel has become an essential part of the lives of many people
today.
With recent research at Manchester University, the
possibility of graphene to be used as a membrane for filtration
is looking more promising. Graphene is known to be a perfect
barrier, meaning it is impermeable to all gases and moistures.
Graphene can even stop helium, the most difficult gas to
block. According to Manchester University, “Graphene oxide
membranes are capable of forming a perfect barrier when
dealing with liquids and gasses. They can effectively separate
organic solvent from water and remove water from a gas
mixture to an exceptional level” [3]. This is an amazing
property to have as a barrier because it can be useful in
filtration. There are current studies looking into the ability to
use graphene oxide membranes in water filtration and
desalination, something that could potentially help solve the
world's water crisis and improve the quality of life of millions
of people.
There are many possibilities for graphene in the area of
energy, including batteries, supercapacitors, and wind and
solar power storage. According to Graphenea, graphene’s high
conductivity gives it the ability to offer much higher storage
capacities with much better longevity and charge rate [1]. Due
to this capability, it is possible that graphene batteries could
soon be replacing traditional lithium ion batteries. Flexible
and extremely lightweight batteries could also be in the near
future with the help of graphene. According to the University
of Manchester, batteries could be so flexible and lightweight
that they could be stitched in clothing and possibly the body.
The example of lightweight batteries is significant for many
applications. Significant impact would be made for soldiers if
they could have batteries stitched into their clothing, reducing
the weight load they’d have to carry around all day essentially
giving them more energy to stay out in the field longer [3].
These batteries could also potentially be rechargeable by the
sun or body heat, which could be useful not only in this
application, but in many others as well. It is said that graphene
batteries are to have a lifetime four times longer than
conventional batteries. This will lead to a reduction in battery
waste, making graphene batteries sustainable.
Graphene’s high conductivity can also lead to many
applications and advancements in electronics such as
smartphones, transistors, and semiconductors. One interesting
application for graphene is flexible electronics that could
Potential as a Drug Delivery System
Drug delivery is an extremely important component of
today’s medicine because it is not simple to transport drugs
through the many barriers they encounter through the body.
According to the American Association for the Advancement
of Science, some critical barriers include rapid filtration in the
kidney for drugs that spend a lot of time in the bloodstream,
the plasma membrane at the tissue or cellular target, and the
harsh acidic environment of endolysosomes. Other barriers
are the nuclear membrane and the multiple drug resistance
mechanisms that pathological cells can develop [8]. With the
many barriers and obstacles drug delivery vehicles must
overcome, it takes a special nanomaterial with specific
properties to be effective in drug delivery.
The most interesting, and even groundbreaking possible
application for graphene is in its potential as a drug delivery
system. CNTs, or carbon nanotubes, are currently being
researched as drug delivery vehicles, but they have some
disadvantages. According to an article on graphene and
graphene oxide as nanocarriers in drug delivery, “Compared
with CNTs, graphene exhibits some important qualities such
as low cost, facile fabrication and modification, a higher
surface area with two external surfaces and the absence of
toxic metal particles. Thus, graphene has begun to threaten the
dominance of CNTs in many applications, including drug
delivery, demonstrating lower toxicity and superior
biocompatibility” [2]. CNTs are rolled, 1-D graphitic
materials, which are a carbon derivative such as graphene, and
can be seen in Figure 3.
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It has also been found that graphene is responsive to
many different stimuli including pH, redox, light, magnetics,
and temperature [10]. This response is very important because
different drugs are best controlled by different stimuli.
Graphene can specifically target tumors more accurately than
other drug delivery vehicles; therefore, graphene is especially
suitable for delivery of anticancer drugs.
CURRENT CANCER TREATMENT
Current cancer treatment options have been around for
the past fifty years. A patient’s type of cancer and how
advanced it is determines the type of treatments they receive
[11]. Some people go through many different types of
treatments, such as surgery, radiation, and chemotherapy.
Other patients participate in clinical trials or research studies.
Additionally, each cancer treatment has its own short and long
term effects. Side effects vary from patient to patient. Some
people have few side effects and some have many. Factors that
can determine the side effects a patient experiences include
age, additional health conditions, frequency of treatment, and
type of treatment [12]. Common side effects include anemia,
appetite loss, bruising, constipation, delirium diarrhea,
fatigue, hair loss, infection, memory loss, nausea and
vomiting, nerve issues, sexual and fertility problems, changes
in skin and nails, sleep problems, and urinary and bladder
problems [12].
One of the most common cancer treatment forms is
surgery. Surgery is often used in combination with other
treatment options. During surgery, the surgeon attempts to
remove the cancerous tumor from the body. There are options
of performing surgery that do not involve cuts with scalpels.
These options include cryosurgery, lasers, and hyperthermia
[11]. Cryosurgery involves using liquid nitrogen to destroy
abnormal tissue. It is often used to treat early-stage skin cancer
and precancerous growths on the skin and cervix. Lasers
involve using powerful beams of light to cut through tissue
and can focus accurately on small areas. This method is
helpful in treating tumors on the skin or on the inside lining of
internal organs [11]. Hyperthermia involves exposing body
tissue to a high temperature in order to damage and kill cancer
cells. This technique helps to make the cells more sensitive to
radiation and chemotherapy. Surgery tends to work best for
solid tumors contained in one area of the body. Because
surgery is a local treatment, it cannot be used for blood cancers
such as leukemia or cancers that have spread to other areas of
the body.
Radiation therapy uses high doses of radiation to kill
cancer cells and shrink tumors. The two types of radiation
therapy are external beam and internal radiation therapy [11].
External beam radiation therapy comes from a machine and
does not touch the body but sends radiation to a specific part
of the body from many directions. Internal radiation therapy
involves inserting either a solid or liquid source of radiation
into the body. Radiation is often used along with surgery in
FIGURE 3 [8]
Carbon nanotubes (CNTs) vs. Graphene
Although graphene and CNTs are similar in some ways,
their differences give graphene an advantage and better
biocompatibility for drug delivery. Graphene’s large surface
area allows for higher drug loading than other nanomaterials,
such as CNTs. Higher drug loading refers to graphene’s ability
to carry more of the drug, therefore increasing its efficiency.
Graphene oxide shows many of the same properties as
graphene and also seems suitable for drug delivery. As shown
in Figure 4, both graphene and graphene oxide can be
multifunctional nanocarriers, carrying the drug, antibody and
imaging probe.
FIGURE 4 [2]
Graphene and Graphene Oxide as Nanocarriers
Drug carriers must have the ability to achieve high
targeting concentration and efficiency at tumor sites. Many
nanocarriers currently being used do not have this ability due
to their limited drug loading capacity. Such disadvantages lead
to a decreased effect of the anti-tumor drug. Along with the
inability to specifically target the placement of the drug comes
the accumulation of the drug in normal tissue, leading to
serious side-effects and limiting the clinical use of some
nanocarriers [2]. None of these disadvantages of current
nanocarriers have been found in graphene or graphene oxide.
According to IEEE, many drug delivery systems tend to
use magnetic particles because they are effective, but
sometimes they cannot be used because they can be toxic in
certain physiological conditions. One property that graphene
does not have is magnetism [8]. This property combined with
the fact that graphene can be changed into spherical liquid
crystal droplets simply and inexpensively, strengthens the
outlook for graphene’s drug delivery potential.
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order to help shrink the cancer prior to surgery or to kill any
remaining cancer cells after surgery has been performed [11].
Radiation therapy often damages healthy cells which
causes the side effects. Patients often have fatigue, hair loss,
nausea, and skin changes. Other side effects often depend on
which areas of the body are being targeted by radiation.
Treatment of the chest, head, and neck often result in issues
with swelling, cough, and changes in the mouth. Radiation of
the stomach, pelvis or rectum can result in diarrhea, bladder
issues, and sexuality and fertility problems [11]. “Healthy
cells that are damaged during radiation treatment almost
always recover after treatment is over. But sometimes side
effects are severe and do not improve” [11].
Chemotherapy is one of the most well-known forms of
cancer treatment. It involves the use of drugs to stop or slow
the growth of cancer cells. Chemotherapy can help to make a
tumor smaller prior to surgery or radiation and also destroy
remaining cancer cells after treatment with surgery or
radiation. Chemotherapy is often used repeatedly to kill cancer
cells that have returned or spread to other areas of the body
[11]. Chemotherapy is most often given through an IV. Other
forms include pills, injections, or topical creams.
Like radiation, chemotherapy often “kills or slows the
growth of healthy cells that grow and divide quickly” [11].
Cells that are often affected include cheek, intestines, and the
cells that cause hair growth. Because of the cells affected, side
effects often include mouth sores, nausea, and hair loss.
Another common side effect is fatigue. Most often, side
effects go away once treatment is over.
Less common forms of cancer treatment include
immunotherapy, targeted therapy, precision medicine,
hormone therapy, and stem cell transplants. Immunotherapy is
a type of biological therapy used to help your immune system
fight cancer. “Biological therapy is a type of treatment that
uses substances made from living organisms to treat cancer”
[11]. Targeted therapy is the foundation for precision
medicine, a newer form of treatment. It targets the changes in
cancer cells in order to provide an individualized treatment for
each patient. Precision medicine helps patients based on
genetic background. Targeted therapy and precision medicine
are not common treatment options yet but doctors hope to
make it a part of routine care soon [11]. Hormone therapy
slows and stops the growth of prostate and breast cancers
which use hormones to grow [11]. Stem cell transplants
restore patients’ stem cells that have been destroyed by
chemotherapy and radiation therapy. Stem cell transplants do
not work to fight cancer directly, but to help a patient recover
[11].
Immunotherapy has many different side effects. The
most common side effects are a result of skin reactions at the
needle site [11]. Side effects include pain, swelling, soreness,
redness, itchiness, and rashes. There are also flu-like
symptoms such as fever, chills, weakness, dizziness, nausea,
muscle or joint aches, fatigue, headaches, breathing issues,
and changes in blood pressure. Less common side effects
include weight gain, heart palpitations, sinus congestion,
diarrhea and risk of infection [11].
Targeted therapy has many side effects. The most
common are diarrhea and liver problems. Others include
problems with blood clotting, high blood pressure, fatigue,
mouth sores, loss of hair color, and skin problems such as rash
or dry skin. “Very rarely, a hole might form through the wall
of the esophagus, stomach, small intestine, large bowel,
rectum, or gallbladder” [11]. There are medicines for these
side effect to help prevent them or to treat them once they
arise.
Hormone therapy causes unwanted side effects because
it blocks the body’s ability to produce hormones. The side
effects vary from person to person. When being treated for
prostate cancer, men will often experience hot flashes, sexual
dysfunction, weakened bones, diarrhea, nausea, and fatigue.
Women being treated for breast cancer often experience hot
flashes, changes in their menstrual cycles, nausea, mood
changes, and fatigue [11].
There are many different types of cancer treatments
available to patients. Each option has its own benefits and
specific uses. As a cancer patient, finding the right treatment
often is a difficult process that involves considering different
factors such as medical costs, but most importantly, side
effects.
Medical researchers at the University of Manchester and
University of Calabria found that graphene can be used as a
cancer treatment, and not just as a drug delivery system [13].
This will be discussed in further detail in a later section. These
researchers found that because graphene oxide forms spheres,
the graphene oxide solution could interrupt the ability of
cancer stem cells (CSCs) to proliferate. This prevents the
CSCs from ever creating tumors in the future [13]. Thus, using
graphene as a cancer treatment would eliminate cancer
recurrence that is common with current treatment options.
Because graphene oxide has not been used in clinical trials,
harmful side effects are not yet known. But, results “show that
graphene oxide is not toxic to healthy cells, which suggests
that this treatment is likely to have fewer side-effects if used
as an anti-cancer therapy” [14].
GRAPHENE AND CANCER TREATMENT
Drug Delivery Properties of Graphene
Current cancer treatments have severe side effects and
show limited therapeutic responses. Therefore, various drug
delivery systems, including that of graphene, have been
explored, aiming at cancer-targeted delivery and controlled
release of therapeutic agents. Graphene has attracted attention
as a possible drug delivery system due to its “intrinsic physical
and chemical properties” [10].
Because of graphene’s high specific area, it can be
loaded with various types of biomolecules that are applicable
in drug delivery and gene transfection [10]. Inorganic
nanoparticles can be anchored to the surface on nano-graphene
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to offer additional optical and magnetic properties which can
be useful for in vivo tumor multimodal imaging. In vivo tumor
multimodal imaging is a tissue imaging technique that
involves two or more imaging techniques in one examination.
Although nano-graphene is toxic, an engineered surface
coating exhibited no obvious toxic effect to a study on mice
[10]. Taking advantage of nano-graphene’s chemical
properties, graphene-based drug delivery systems can be
responsive to a number of stimuli such as pH, redox potential,
biomolecules, near infrared (NIR) light radiation, magnetic
field, and temperature [10].
Graphene-based drug delivery systems responsiveness
to pH, redox potential, and biomolecules of interest “have
been widely developed to enhance therapeutic efficacy and
reduce side effects” [10]. pH sensitive drug delivery systems
are responsive to abnormal changes in pH values in cancer
sites. Tumor sites are more acidic than healthy tissues, so
acidic sensitive drug delivery systems are effective. By
coating the surface of nano-graphene, graphene can be used
for loading anticancer drugs and pH dependent drug release
[10]. In order to improve therapeutic efficiency and reduce
side effects, ligands have been used with graphene-based drug
delivery systems. Additionally, pH responsive graphenebased drug delivery systems have been found to enhance the
efficacy of chemotherapy [10].
Cellular redox environment is mainly regulated by levels
of glutathione (GSH). GSH is a compound present in the
cytoplasm of cells with high concentrations [10]. Deficiency
in GSH levels leads to increased oxidative stress, while an
excess increases resistance to oxidative stress. Oxidative
stress is an imbalance between the production of reactive
oxygen and the body’s ability to repair its harmful effects
through neutralization [10].
Combined GSH and graphene oxide based nanocarriers
have been proven to “significantly improve the killing
efficiency against cancer cells” [10]. In addition to redox
responsive surface modification of graphene to enable drug
release, it was found that biodegradation behaviors of
graphene oxide could be regulated by its redox-sensitive
surface coating. In a recent work by Zhen Gu, a professor in
the Biomedical Engineering Department at University of
North Carolina Chapel Hill, adenosine triphosphate (ATP),
the primary energy source of cells, was used as an intracellular
trigger to enhance the release of the loaded drug from
graphene oxide nanocarriers. Gu found that due to this,
graphene oxide could offer “synergistic antitumor activity”
[10].
Photothermal therapy (PTT) has been widely used to
directly kill cancer cells using optical-absorbing nano-agents,
which could generate heat under near infrared light irradiation.
PTT is the use of electromagnetic radiation to treat cancer
[10]. Many inorganic and organic nano-agents, including
nano-graphene, have been deemed as efficient photothermal
agents for direct photothermal removal of cancers [10]. Owing
to the intrinsic high photothermal conversion ability of nanographene, NIR laser irradiation could also be used to enhance
drug release from the nano-carrier, realizing photothermally
triggered drug release [10]. In the past few years, graphenebased nanoparticles with magnetic properties have also been
used for drug delivery. In research done by Xiaoying Yang,
Associate Professor in the School of Pharmaceutical Sciences
at Tianjin Medical University, it was found that cancer
attacked with a graphene oxide based drug delivery system
under a magnetic field showed high drug intake [10].
Thermal effect has also been shown to be a useful
stimulus for graphene-based drug delivery. Therefore,
graphene-based drug delivery systems containing thermosensitive polymers may be used as nano-carriers responding
to temperature changes, which could be induced by directly
heating or by indirect hyperthermia effects such as
photothermal and magnetic [10]. Graphene-based drug
delivery systems responding to stimuli such as pH, redox and
biomolecules have been widely explored to realize cancerspecific drug delivery, by taking advantage of the acidic tumor
environment and the high intracellular GSH level. With strong
NIR absorbance, graphene has been widely explored for NIRresponsive drug delivery [10]. Whether graphene is unique
here or may be replaced by other conventional drug carriers
for these applications is still unknown.
Clinical Trials at the University of Manchester
Cancer stem cells (CSCs) are “immortal, divide rapidly,
and are highly resistant to conventional treatments” [13].
CSCs are also responsible for the spreading of cancer,
therefore the targeting of them is critical to the health of cancer
patients. Dr. Aravind Vijayaraghavan and Professor Michael
Lisanti at the Institute of Cancer Sciences at the University of
Manchester began investigating the potential of graphene as a
cancer treatment option.
The research team ran tests to see how six types of CSCs,
breast, pancreatic, lung, brain, ovarian, and prostate, reacted
when subjected to graphene oxide [13]. The CSCs were
treated with graphene oxide solution for 48 hours. It was found
that graphene oxide interrupted the ability of CSCs in each
cancer type to “proliferate by forming spheres, and forced
them to differentiate into non-cancer stem cells” [13]. This
prevents the CSCs from ever creating tumors in the future. It
is not yet clear why this is true, but a current theory is that the
graphene oxide interferes with the pathways in the cell
membranes, stopping the proliferation mechanism [13]. The
graphene oxide did not harm any healthy cells either. This
medical discovery must be better understood before it can
become a cancer treatment option. However, graphene’s
ability to destroy CSCs without destroying healthy tissue is an
important component of cancer treatment.
SUSTAINABILITY OF GRAPHENE
Sustainability is a word that can have many different
meanings, and graphene falls under many of those definitions.
According to the University of California, Los Angeles,
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sustainable development is development that meets the needs
of the present without compromising the ability of future
generations to meet their own needs, particularly with regard
to use and waste of natural resources. Sustainability assumes
that resources are limited and should be conserved.
Sustainable practices support ecological, human, and
economic health and vitality [15]. Graphene will be helpful in
the future in eliminating glass and plastic waste from
smartphones and electronics. Also, graphene will be
sustainable in batteries by reducing battery waste as well.
Maybe the most sustainable use graphene will be used for is
in drug delivery.
One specific meaning of sustainability that can be
applied to graphene is quality of life. Graphene is sustainable
in drug delivery because it will improve the quality of life of
the patients receiving drugs delivered by graphene. Graphene
drug delivery will be more efficient and effective than current
methods being used. Graphene’s potential to deliver anticancer drugs will immensely improve the quality of life of
cancer patients and their families. With cancer being one of
the greatest healthcare problems of today, improved anticancer drug delivery with a sustainable nanomaterial such as
graphene will have an impact on society because most people
know somebody that has or has had cancer.
SOURCES
[1] J. La Fuente. “Graphene Applications & Uses.”
Graphenea.
Accessed
1.10.2017.
http://www.graphenea.com/pages/graphene-usesapplications#.WHMHAIWcHgA
[2] J. Liu, L. Cui, D. Losic. “Graphene and graphene oxide as
new nanocarriers for drug delivery applications.” Acta
Biomaterialia.
2013.
Accessed
1.8.2017. http://www.sciencedirect.com/science/article/pii/S
174270611300408X. pp. 9243-9257
[3] “The Home of Graphene.” The University of Manchester.
Accessed 2.9.2017. http://www.graphene.manchester.ac.uk/
[4] “Graphenes, Graphene Oxides (GO),” TCI America.
Accessed
2.28.17.
http://www.tcichemicals.com/eshop/en/us/category_index/12
962/
[5] A. Geim, S. Morozov, K, Novoselov. “Electric Field Effect
in Atomically Thin Carbon Films.” Association for the
Advancement of Science. 2004. Accessed 3.2.17.
http://science.sciencemag.org/content/306/5696/666
[6] “Graphene- the perfect atomic lattice.” Royal Swedish
Academy of the Sciences. 2010. Accessed 3.2.17.
http://www.nobelprize.org/nobel_prizes/physics/laureates/20
10/popular-physicsprize2010.pdf
[7] D. Johnson. “Graphene transforms itself into a sphere for
drug delivery.” IEEE Spectrum. 2014. Accessed
1.8.2017.http://spectrum.ieee.org/nanoclast/biomedical/devic
es/graphene-transforms-itself-into-a-sphere-opening-upmedical-applications
[8] A. Chilkoti, J. Hubbell. “Nanomaterials for Drug
Delivery.” American Association for the Advancement of
Science.
Accessed
2.28.17.
http://science.sciencemag.org/content/337/6092/303.full
[9] “CNT & Graphene Chemistry.” Department of Chemistry,
Kookmin
University.
2011.
Accessed
3.1.2017.
http://polymer.kookmin.ac.kr/research/research.php
[10] K. Yang, L. Feng, Z. Liu. “Stimuli responsive drug
delivery systems based on nano-graphene for cancer therapy.”
Advanced Drug Delivery Reviews. 2016. Accessed
1.11.2017.
http://www.sciencedirect.com/science/article/pii/S0169409X
16301570. pp. 228-241.
[11] “Cancer Treatment.” National Cancer Institute.
4.29.2015.
Accessed
2.9.2017.
https://www.cancer.gov/about-cancer/treatment
[12] “Side Effects.” National Cancer Institute. 4.29.2015.
Accessed
2.9.2017.
https://www.cancer.gov/aboutcancer/treatment/side-effects
[13] M. Williams. “Graphene used to fight cancer.” HeroX.
2015. Accessed 1.10.2017. https://herox.com/news/240graphene-used-to-fight-cancer
[14] “Graphene shows potential as novel anti-cancer
therapeutic strategy.” The University of Manchester.
2.25.2015.
Accessed
3.27.17.
THE FUTURE OF GRAPHENE AS A DRUG
DELIVERY SYSTEM
Graphene has many unique properties and has found its
application among many areas of society. Among these areas,
drug delivery for cancer treatment may soon be one of them
because there are many problems with current cancer
treatments. From recent research, it has been found that
graphene as a drug delivery system for cancer treatment may
reduce some of these problems, such as late effects of cancer
treatment and recurrence. Some of graphene’s properties that
would make it a successful drug delivery system include its
large surface area, large drug loading capacity, ability to
transform into a spherical form and responsiveness to many
different stimuli great for drug delivery including pH, redox,
light, magnetics, and temperature [10]. Despite encouraging
pre-clinical results reported in recent years, graphene-based
drug-delivery is still challenging. Understanding the potential
toxicity and degradation behavior of graphene is most
important for further development of graphene-based drug
delivery systems [10]. Graphene without surface coating
would cause significant toxicity to cells. Although it is well
documented that nano-graphene with ultra-small sizes and
biocompatible surface coatings appear to be quite safe in vitro
to cells [10]. Therefore, major efforts are still needed to
persuade the public to accept the use of graphene-based drug
delivery systems in the clinic.
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Taylor Daniels
Jessica Sorick
http://www.manchester.ac.uk/discover/news/grapheneshows-potential-as-novel-anti-cancer-therapeutic-strategy
[15] “What is Sustainability?” University of California, Los
Angeles.
Accessed
3.26.2017.
https://www.sustain.ucla.edu/about-us/what-issustainability/
ACKNOWLEDGEMENTS
We would like to thank our writing instructor, Keely
Bowers, the freshman engineering writing program director,
Beth Newborg, and our conference co-chair, Abigail
Kulhanek, for their guidance, feedback and support. Also,
many thanks to Judith Brink and Ashley Sowa, the librarians
at the Bevier Engineering Library, for their help with research
advice for our topic.
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