Session A13
2298
NANOPARTICLES USED IN CANCER THERAPY TO TARGET TUMORS
Jill Palski (jcp60@pitt.edu), Nathan Budny (ndb36@pitt.edu)
Abstract— Nanotechnology, though not a new concept,
shows great promise in many engineering fields.
Nanoparticles in particular have become especially
important in the fields of biology and medicine. This paper
will describe and evaluate the revolutionary use of
nanoparticles, especially gold nanoparticles, as a means of
suppressing cancer cells in cancer therapy. Alternative
cancer therapies will be briefly assessed and shown why
they are inferior to nanoparticle therapy. The methods and
uses of nanoparticles in cancer therapy will be introduced
and the importance of a specific type of nanoparticle, gold
nanorods, will be explained. The advantage of using these
gold nanoparticles will be discussed in great detail with an
attention put on their specific abilities that make them more
effective than other nanoparticles. Also, the positive social
implications of using nanoparticles as cancer therapy will
then be discussed. Nanoparticles like gold nanorods, due to
their size, allow for better penetration of the drug through
tissue into the affected cells at a reduced risk, in comparison
to the conventional cancer therapies. The use of
nanoparticles allows for a lower dosage of a particular
medicine which would minimize dangerous side effects while
maintaining initial efficacy. Nanoparticles are a promising
and critical component of precise drug administration.
drug delivery systems. Within cancer therapy they present a
potential to drastically reduce the harmful effects of
conventional cancer therapy. Conventional cancer therapy
like chemotherapy is very effective in destroying tumor cells
but can also destroy and damage other cells within the body.
The advantage of using nanoparticles is that the drug
delivery system allows the drug to get to the tumor cell
without harming other parts of the body, where previous
drug delivery methods didn’t fully prevent the drug from
escaping through the veins and affecting other parts body.
One specific type of nanoparticle that researchers have been
developing is gold nanoparticles which can be used to better
target and destroy tumor cells.
Typically, nanoparticles are defined as tiny particles
ranging in size of 1 nanometer to 100 nanometers, to put that
in perspective the average human is about 80,000
nanometers wide [2]. When used in medicine and drug
delivery, the particle can be engineered to contain a drug that
is either completely encapsulated in the particle or attached
to one of the polymer layers of the nanoparticle [3].
Engineers have the power to manipulate the nanoparticles to
perform a particular function desired to help treat cancer.
One of the major perks when designing nanoparticles is the
ability of control. Designers can control the particle size,
surface properties, polymer layers, and release of the
therapeutic medicine [3]. With this control, engineers are
able to enhance cancer treatment when used in conjunction
with the conventional cancer therapies.
Key Words— cancer therapy, gold nanorods, nanoparticles,
polymer coating, targeting
NANOPARTICLES IN THERAPY
CONVENTIONAL CANCER TREATMENTS
For years engineers have been faced with challenges in the
chemical and medical field. Mike Davis, a chemical
engineer from the California Institute of Technology, was
given unexpected challenge when his wife was diagnosed
with breast cancer. After seeing the struggles his wife
experienced while receiving chemotherapy, he changed his
line of work from the oil industry to the medical field and
focused on the development of a drug that would reduce the
side effects of chemotherapy and potentially lead to the cure
of cancer using nanoparticle technology. Eventually, his
research lead him to the creation of a new drug delivery
system in which he filled tiny spheres made from sugar with
hundreds of cancer drug molecules. This ensured that none
of the cancer drug molecules would escape into the blood
stream and harm the healthy cells in the body [1]. This is just
one example of the positive effects of using nanoparticles in
cancer therapy.
Nanoparticles have been effective in many fields of
medicine for quite some time. But of recent years their true
potential has been discovered, by realizing how the use of
such small particles could allow for better and more efficient
The typical cancer treatments are extremely effective in
destroying cancer cells, yet have severe side effects. Two
popular treatments are radiation and chemotherapy, which
are reputable for giving the patient negavtive side effects.
Radation kills cancer cells by directly attacking tumors and
damages their cells with high energy radiation beams.
Chemotherapy is a term used for a variety of drugs which
attack rapidly dividing cells and prevent further reproduction
[4]. These treatments can often be used in conjuntion with
eachother as an effective therapy. While extremely effective,
the treatments are often not very efficient because the
treatments lack a means of targeting the tumor cells. Both
methods end up damaging healthy cells as the cancer cells
are attacked which causes the negative side effects. These
side effects can be things from hair lose, bone marrow lose,
digestive problems, nausea, lack of energy, and mouth
ulcers. For Mike Davis’ wife the side effect was the permant
loss of most of her hearing. These side effects can
potentially be so severe that some patients choose to forgo
treatment [5]. In addtion to damaging other cells and causing
University of Pittsburgh
Swanson School of Engineering
April 14, 2012
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Jill Palski
Nathan Budny
terrible side effects this methods can often drag on for a very
long period and become very expensive. If the inclusion of
nanoparticles in cancer therapy could increase the efficiency
of treatments, these patients could agree to the treatment and
potentially save their lives.
Several nanoparticle chemotherapy drugs are in clinical
trials and hold great potential to improve the chemotherapy
[6]. These nanoparticles in clinical trials may be delivered to
the tumor via active targeting, which selectively accumulates
at the tumor cells and delivers the anticancer treatment. The
nanoparticles are developed to target certain characteristics
of the tumors, such as their low pH, which reduces the drug
exposure to healthy tissues [2, 3]. In cancer therapy,
targeting and recognizing the harmful cells increases the
accuracy of the treatment and reduces the toxicity to healthy
cells which diminishes the severe side effects.
NANOPARTICLES IN CANCER THERAPY
Nanoparticles have become a vital aspect of nanotechnology
and the medical field. There has been considerable research
done on drug delivery using nanoparticles as the drug carrier
which has led to a method of incorporating these
nanoparticles in cancer therapy. Research has developed
several different applications of nanoparticles to therapy
including diagnosis and imaging. An emphasis will be
placed on applications of radiotherapy and targeted
chemotherapeutic drug delivery in cancer therapy.
Effect of Particle Size on Drug Delivery
The use of nanoparticles in drug delivery systems for cancer
therapy has a positive impact on treatment including better
penetration of the therapeutic drug at a reduced risk [2]. The
small particle size is an important characteristic which
allows for a wide distribution throughout the body and a
longer circulation time which gives a greater potential of the
particles finding the tumor and accumulating to deliver the
medicine [3]. Nanoparticles smaller than 20 nanometers
wide are able to easily travel through the body and pass
through the blood vessel walls to reach the tumor and
interact with the tumor cell surfaces [2]. These features
allow for an effective arrival of treatment and cancer therapy
to the tumor, and the small size also contributes to the
administration of the drug. Small particles have a relatively
larger surface area than large particles, and the small size
also places the drug closer to the edge of the particle [3].
These features both lead to a fast and efficient drug release
which increases the effectiveness of the drug delivery
system.
FIGURE 1
THE FIGURE DEMONSTRATES THE NANOPARTICLES ACTIVELY TARGETING
THE CANCER CELLS WHILE AVOIDING THE NORMAL CELL. [2]
A company in Massachusetts named BIND Biosciences has
developed a drug delivery system that diminishes the side
effects of chemotherapy [5]. Their particles are made to
remain in the blood stream for more than a day, which
increases the potential of the drug to reach the tumor, and
contain tumor-targeting proteins which are attracted to
prostrate, breast, and lung tumors in rodents. The company
recognizes that some patients choose to forgo chemotherapy
because of its harsh side effects. Their particles, which
reduce the dose while maintaining its efficiency, will allow
for these patients to be treated without being exposed to the
extreme toxicity [5].
Aside from chemotherapy, radiotherapy is a process of
using radiation to treat cancer. Cancer cells lack mechanisms
for repairing DNA breakage, so when radiation is applied to
tissues, healthy cells are able to repair themselves leaving
the cancer cells damaged and unable to reproduce as rapidly
[2]. However, this process is not completely harmless to the
normal, healthy cells. But the inclusion of nanoparticles
serving as radio sensitizers in treatment enhances the
effectiveness of radiation.
Gold nanoparticles developed as radio sensitizers are
designed to enhance radiotherapy by decreasing the dose
which decreases the damage to surrounding healthy tissues,
while promoting the elimination of cancerous tissues [2].
These gold particles are equipped with specific targeting
Use with Chemotherapy
Chemotherapeutic drugs target fast growing tumor cells and
inhibit the rapid cell division process. Chemotherapy is an
extremely effective method of treating cancer, but
oncologists must be extremely careful when administering
the treatment due to the severe side effects. A successful
treatment depends on a sufficient amount of drug delivered
while minimizing the toxic side effects on the patient [2].
Incorporating nanoparticles into chemotherapy presents a far
more effective treatment than conventional chemotherapy;
the use of small nanoparticles in chemotherapy decreases the
dosage while maintaining its treatment of cancerous tumors.
[2]. The smaller dosage of the drug dramatically decreases
the potential of harmful side effects, which allows for the
patient to receive the proper amount of treatment without
having to suffer with the severe side effects.
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capabilities which allow the particles to accumulate at the
tumor and avoid the normal tissues. When the tumor is
treated with radiation, results show that 86% of tumors were
reduced in size when surrounded by the gold nanoparticles
compared to 20% reduction when treated with radiation
alone [2]. These gold nanoparticles will be discussed in
detail in the succeeding section. The inclusion of the
nanoparticles in radiation increases the effectiveness of the
therapy which is beneficial to the patient by decreasing the
amount of radiotherapy needed to treat the tumor.
causing the cancer cells surrounded by these nanoparticles to
glow [2]. This allows doctors and surgeons to clearly locate
the tumor and distinguish between the cancer cells and the
healthy cells. The contrast agents also permit a real-time
monitoring of the tumor [2]. The inclusion of gold
nanoparticles in imaging systems allows for more accurate
and sensitive readings, and thus allows the doctors to
accurately diagnose the tumor at an early stage.
GOLD NANOPARTICLES
Gold nanoparticles are just one example of the many
nanoparticles used in nanomedicine and cancer therapy.
Because the material is multifunctional, gold nanoparticles
are gaining popularity in cancer research and treatment.
These particles are considered relatively non-reactive and
stable, in comparison to the very toxic and reactive silver
and cadmium nanoparticles, and therefore suitable for living
patients [7]. Gold particles also have strong optical
properties due to localized surface plasmon resonance [7].
This allows doctors to more easily seek and identify tumors
and therefore better diagnose. Another positive quality of
gold particles is its surface chemistry is easy to control [7].
Engineers are able to add specific functional layers to the
particle for increased versatility. A final function of gold
particles is the ability to manipulate the size and shape of the
particle [7]. This also increases the versatility of the particle
and allows the designer to specifically create a particle to
perform a certain function. All of these factors contribute to
the strong interest in gold particles in cancer treatment.
FIGURE 2
NANOPARTICLES (PINK) COLLECT IN A PROSTATE CANCER CELL (GREEN,
NUCLEUS IS BLUE) [5]
Once doctors can differentiate between healthy cells and
cancer cells, destroying cancer cells becomes a much easier
task. One form of cancer, hepatocellular carcinoma, the most
common form of liver cancer strikes more than 500,000
people every year, most of who die within six months. The
main reason this cancer is so hard to stop is due to its early
aggressiveness which makes chemotherapy less effective
and surgery much too difficult [1]. But when the cancer is
detected in its early stages it is much easier to solve. This is
made possible by gold nanoparticles which can be used to
detect tumors as small as five centimeters in diameter [1].
Another perk of using gold nanoparticles to identify and
target cancer cells is the price. The use of gold nanorods
costs about one third the price of the similar method of flow
cytomety, which binds fluorescent markers to cancer cells.
But this method requires a bigger sample with many more
cells than when using nanorods. Using nanorods also allows
doctors to observe the samples using a cheaper microscope
and light supply instead of an expensive microscope and
lasers. Overall the use of gold nanorods can cut back on the
price of detecting cancer cells both for the hospitals and the
patients. But what is truly incredible about these gold
nanoparticles is how they can also be used to destroy the
cancer cells in addition to targeting them [9].
Gold Particles in Sensing and Identifying Tumors
Just like other nanoparticles, the drug delivery system for
gold nanoparticles allows the particles to get to the tumor
and destroy it without releasing any of the cancer drugs into
other parts of the body. But what distinguishes these gold
nanoparticles is their ability to scatter and absorb light. This
ability allows these particles to perform many different
functions. First they can be used to target and identify
cancer cells with more accuracy than methods currently
used. Conventional imaging technologies are not sensitive
enough to detect the smallest tumors in its early stages [2].
Early detection is critical for successful treatment of tumors.
Gold nanoparticles can serve as imaging agents to help
identify early stages of cancer.
The particles can be engineered to carry products for
imaging purposes, such as bioluminescent agents. The
particles will then be fitted with antibodies that latch onto
the proteins located on the exterior of cancer cells [8]. This
ensures a large collection of image functional gold particles
which will increase the signal returned to the doctor. Once
concentrated near the tumor and attached to the cells, the
tissue is exposed to infrared light. The gold nanoparticles
absorb the light, then emitting a fluorescence spectrum,
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the particle in various polymer layers. This “layer-by-layer
assembly” approach allows for each polymer layer on the
particle to have a specific purpose and function, which is
essential for the efficient delivery of the drug. Since each
layer can be tailored for a specific function, nanoparticles
could perform virtually any function and carry any type of
drug. This combination allows for nanoparticles to target a
wide variety of tumors.
Gold Nanoparticles in Thermotherapy
When it comes to destroying cancer cells, many methods
have been used over the years, one of which is the simple
inducing hyperthermia to the tumor. The only problem is
that in order to fully wipe out the tumor, it must be heated to
temperatures that are harmful to other nearby cells. But
when using gold nanoparticles, risky side effects are no
longer an issue. After the particles congregate around the
targeted tumor, a radiation beam is exposed through the
tissues [7]. Since gold nanoparticles have the ability to
absorb light, shining a radiation light on the particles causes
the particles absorb and gain energy. The gold particles then
convert a significant amount of the radiation into heat, which
is emitted to the surrounding target tumor [7]. During the
exposure to the near-infrared light, the gold nanoparticles
reach 70 degrees Celsius which is hot enough to destroy
cancer cells [9]. This strong absorbance of light allows for
the strong, rapid, and focused emitting of heat, which is able
to heat the tumor while minimizing the amount of damage
done to the surrounding healthy cells [7]. The rapid
dissipation of energy causes irreversible cell damage as it
denatures the proteins in the cells. All of this damage is
focused to the tumor and avoids disrupting the healthy cells.
With continued research this method could potentially allow
doctors to target and destroy unwanted cancer cells in one
specific and efficient step of sending light to gold
nanoparticles positioned near the tumor.
Layer-by-Layer Study
A research team of chemical engineers from MIT were
inspired by the multifunctional layer-by-layer method and
successfully designed a nanoparticle comprised of several
polymer coatings to target breast cancer cells [10, 11]. Their
approach could theoretically work for other types of
cancerous cells as well [11]. The researchers recognized that
tumors generally have a higher acidity than healthy tissues,
and were able to create a certain system of layers to respond
to the high acidity. Like most other drug-delivering
nanoparticles, the outermost layer of the particle acts as a
protective coating that keeps it from degrading in the blood
stream [10, 12]. Made from poly(ethylene glycol), the
protective layer reacts to the acidic environment of the tumor
and is selectively removed from the particle as the
interactions between the layers are decreased [11]. This
protective layer is essential for not only keeping the
nanoparticle intact until it reaches the tumor, but also for
protecting healthy tissues from the potentially damaging
charged layer underneath this protective layer. Once the next
polymer is exposed, as seen in Figure 4, the positively
charged layer can penetrate into the tumor because the
positive charge is attracted to the negatively charged cell
membrane and allows for easy passage through the tissue
[10]. This innermost layer is then exposed, which can be a
polymer that carries virtually anything the designer wants
including an anti-cancer drug.
FIGURE 4
FIGURE 3
THE POLYMER COATING (LIGHT BLUE) IS SHED AS THE PARTICLE
APPROACHES THE TUMOR, EXPOSING THE POSITIVE CHARGES [12]
GOLD NANORODS ABSORB ENERGY FROM NEAR-INFRARED LIGHT AND EMIT
IT AS HEAT DESTROYING TUMORS [6]
When this layer-by-layer construction was tested in mice,
researchers reported that the particles were able to survive in
the blood stream for up to 24 hours, accumulate at the tumor
site, and successfully enter into the tumor cell [11, 12]. The
long circulation time allows for the particles to have the time
to find the acidic environment of the tumor and accumulate
at the site to deliver the cancer drug. Prolonging the
residence time in the tumor would evidently impact the
clinical use of the drug [11].
POLYMER COATINGS
In order for these nanoparticles to work properly in the body,
chemical engineers are needed to develop ways to produce
the particles to ensure the treatment works efficiently and
properly. Because there are many different variables in
creating nanoparticles, such as the environment of the target
and the purpose of the drug, there is not one correct process
for creating a nanoparticle. A typical means of developing
these nanoparticles for use in drugs and treatment is to coat
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them to be used in a variety of ways; one example is as a
carrier of a drug called paclitaxel. Paclitaxel is one of the
most effective chemotherapeutic drugs for treating various
cancers [15]. However, the drug alone has limited
therapeutic effects due to its toxicity to healthy cells which
is a result of the drug lacking selectivity to cancer cells and
poor water-solubility [15]. This is one example of how
attaching the drug to gold nanoparticles is an effective
means of a drug carrier.
To minimize the toxic side effects of paclitaxel,
researchers introduced a targeted drug delivery system with
cancer-specific receptors to selectively attack the cancer
cells, much like other examples of nanoparticles in cancer
therapy [15]. Their study was based on gold nanoparticles
infused with paclitaxel and biotin receptors and was
evaluated on its effectiveness in the treatment of certain
human breast, lung, and bone cancers.
Their results showed that gold nanoparticles are an
effective targeted drug carrier [15]. They found that the drug
paclitaxel alone had a resulting 67% healthy cell mortality
rate compared to using gold nanoparticles as a carrier [15].
These results show that gold nanoparticles effectively target
and attack tumors without harming normal cells. It was also
found that the biotin receptors induced intracellular uptake
into the tumor cells, which suggests that these receptors are
beneficial in targeting cancer cells [15].
Another example of a targeted drug delivery gold
nanoparticle system is the administration of the drug
tamoxifen. This drug is used for the treatment of breast
cancer and has been used for more than thirty years [16]. By
attaching the drug to gold nanoparticles, research results
show that the tamoxifen has an increased selectivity to tumor
cells as well as a 2.7-times enhanced potency toward killing
the tumor cells [16]. The particles are also equipped with a
time-depended dose release which presents a higher degree
of drug uptake in the cancer cells; results indicate a 1.3-2.7
fold enhanced potency for killing cancer cells [16].
GOLD NANOPARTICLE LAYERS
Gold nanoparticles can be prepared in a similar fashion with
the layer-by-layer approach. Researchers have developed a
multilayer-based drug carrier system for delivering waterinsoluble drugs, like certain cancer drugs [13]. The
photosensitizer mTHPP is an anticancer drug that is
practically insoluble in water and therefore must be
delivered to cancer patients through a painful ethanolic
solution administered intravenously. Another side effect of
the drug is a prolonged sensitivity to light for up to two
weeks after treatment due to accumulation of the drug at
malignant and healthy tissue cells [13]. To overcome these
side effects, researchers developed a promising nanoparticle
based on the layer-by-layer technique, which ensures
maximum flexibility for the drug carrier.
The gold core of these nanoparticles was chosen for
several beneficial reasons. These reasons include the size
range which can be obtained for the drug delivering
particles, and its high chemical stability [13]. Also, gold
nanoparticles reduce adverse effects due to particle toxicity
and are highly compatible with cells and tissues [13, 14].
The uses of gold nanoparticles can also improve the stability
and solubility of the drug which improves its therapeutic
effect [13].
The gold nanoparticle coating consists of several drug
layers to create the multilayer drug delivery system. The
coatings exist for different functions in the gold nanoparticle
system. Many versions of the gold nanoparticles exist, so
there is not one definite system of layering polymer
coatings. Typically, the first layer is deposited onto the gold
particle to facilitate the attachment of the additional layers
[14]. The small gold nanoparticles are a stiff, rod like
molecule, which could potentially pose difficulty for the
subsequent polyelectrolyte layers to be deposited onto the
molecule.
The positive surface charge of one of the poly(ethylene
imine) (PEI) polymer layers guarantees the particles are
attracted to the cell wall and then incorporated into the cell
to deliver the medicine [14].
One of the coatings allows for the nanoparticle system to
be water-soluble after accepting a water-insoluble drug,
which allows for an effective dispensing of the drug into the
body. H-bonds and π−π interactions create a coadsorabte of
the water-insoluble mTHPP and the polyelectrolyte layer
resulting in a stable, water-soluble polymer complex. This
also allows for the drug to avoid a strong reduction in effect
by the covalent binding of mTHPP to the gold surface [13].
The use of this layer-by-layer technique in gold
nanoparticles dramatically increased the efficiency of the
drug delivery, by a factor of 100 [13].
THE FUTURE OF CANCER THERAPY
According to the World Health Organization, cancer claimed
the lives of 7.9 million people in 2007; this number is
expected to grow towards an estimate 12 million deaths in
2030 [7]. These statistics also do not include the millions
that survive the cancer but must live with the numerous
terrible side effects for the rest their lives. The need for
improved cancer treatments is ever increasing to challenge
this increasing statistic. The classic, conventional methods of
treating cancer, e.g. chemotherapy and radiation, are
extremely effective, but have detrimental side effect to
patients because the treatments harm healthy tissue and do
not specifically target the tumor cells. The other common
method of surgically removing the tumor is also flawed in
that it is mostly restricted to large accessible tumors.
Researchers have been developing a system that uses
nanoparticles to target and attack the cancer cells effectively
EXAMPLES OF ANTI-CANCER DRUGS
Gold nanoparticles have been used extensively as drug
carriers and in cancer cell targeting. Their stability allows
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Nathan Budny
Formulation
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and efficiently. These nanoparticles are equipped with
various tumor-seeking methods which increases the
likelihood that the drug will be administered properly to the
tumor.
While there are countless varieties and types of
nanoparticles, the method of layer-by-layer construction
presents a promising means of developing these drug
carrying particles. The creators are able to specifically adapt
each layer for a certain purpose in delivering the medicine to
the tumor, such as protecting the particle or carrying a
charge to be attracted to the tumor cell walls.
There are many different types of nanoparticles used in
cancer treatment, in particular, gold nanoparticles are
multifunctional and have the ability to be applied to several
different aspects of treatment, including radiotherapy and as
a chemotherapeutic drug carrier. When used in radiotherapy,
these particles increase the potency of the radiation applied
to the tumor which makes the treatment more efficient by
focusing the radiation to the tumor and minimizing the effect
on the healthy tissues. When used as a targeting drug carrier,
the gold nanoparticles can be developed with several
different layers, each created for a specific purpose.
There are numerous studies and clinical trials focusing
on the use of nanoparticles in treating cancer. These trials
are finding a promising future for the use of gold
nanoparticles in cancer treatment. With continued research
and trials, the use of nanoparticles could become the
conventional means of efficiently treating cancer.
Cancer has been a disease that has riveted our world for
hundreds of years. It takes the lives of millions of people
each and every year. For centuries people have been
searching for a cure to this terrible disease. Though an exact
cure might never be found, the use of nanoparticles is one
large step in the right direction. These particles, especially
gold nanorods, combined with the current methods for
cancer treatment could drastically reduce the amount of
people taken every year by this horrible disease. With
continued research and advancements in these particles
curing cancer may no longer be something that seems
impossible.
ACKNOWLEDGMENTS
REFERENCES
We would like to thank Judith Brink and the library for
helping with the research aspect of this paper. Also, we
would like to thank Professor Budny for helping us with
editing and wonderful insight.
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Nanoparticles in Cancer Therapy.” Recent Patents on Drug Delivery &
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