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Blake Zucco
Chawkat
Independent Research 3
8 April 2016
Tamoxifen-Poly(ethylene glycol)-Thiol Gold Nanoparticle Conjugates: Enhanced Potency and
Selective Delivery for Breast Cancer Treatment
Breast cancer is traditionally treated with radiation or chemotherapy, but gold
nanoparticles could be used to increase the effectiveness of chemotherpay in targeting breast
cancer tumors and delivering the antiestrogen compounds to the tumors. Traditionally,
antiestrogen compounds are injected into the body and passively diffuse into estrogen
recptors(ER). Tamoxifen (TAM) is one of the antiestrogen compounds commonly used to diffuse
into ER and kill the cell by preventing the adoption of important cofactors the cell needs to
survive. All breast cells produce ER, but breast cancer cells over express these hormones 75-80%
allowing TAM to more easily diffuse into cancerous cells however TAM may diffuse into healthy
cells and destroy them as well. In order to prevent healthy cell destruction, TAM delivered by
gold nanoparticle endocytosis which allows for more selective diffusion and delivery to
overactive, cancerous cells. ER is located on the membrane and within the malignant cell itself
allowing for TAM attached to gold nanopaticles to permeate and enter the cell easier. The ER
naturally attracts a steroidal hormone(E2) to provide a growth factor for the cell to survive. The
two compounds both seek to bind to ER, so the two compounds compete to bind to the open ER
sites. Without enhanced targeting and binding provided by the gold nanoparticles, TAM is unable
to bind to a relatively large number of cancerous cells reducing its effectiveness. In the in vitro
experiment, TAM attached to gold nanoparticles and passively diffusing TAM are observed.
Microscopy results of the in vitro experiment show that TAM accompanied by gold nanoparticles

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is 1.3-2.7 fold more effective than passively diffusing TAM. In addition, breast cells exposed to
estrogen prior to exposure to TAM saw a significant decrease in the viability of the drug. The
addition of gold nanoparticles to TAM increases its ability to compete with estrogen in binding to
ER sites. The increased rate of the drug and nanoparticle's transportation caused a noticeable
shift in augmented potency of TAM as opposed to the slower delivery of the free drug Tam.
Although the journal goes deeper into detail regarding the process and steps of the
experiment, the article provided important information regarding the effect the gold nanoparticle
has on the delivery of common chemotherapy methods. The study found that the gold
nanoparticle increased the effectiveness of drug transportation, but the nanoparticle also
increases the drug's viability to bind to receptors after they are exposed to other compounds such
as estrogen. Cells were incubated for multiple durations up to 48 hours exposing them to other
proteins and compounds that were not TAM. The experiment showed that TAM attached to gold
nanoparticles decresed in viability much slower than TAM as a free drug. The increased potency
of TAM accompanied by gold nanoparticles implicates that chemotherapy treatments benefit and
are more effective when bound to gold nanoparticles used for intracellular transport. The study
also creates a new dimension of benefits of gold nanoparticle drug delivery, for they increase the
effectiveness of chemotherapy drugs over an extended period of time.
The information provided in the jurnal strengthens my hypothesis further reinforcing the
idea that traditional methods are more effective when combined with gold nanoparticles. The
nanoparticles increase overall potency and the viability of the drugs to bind to specific receptors.
Although the journal supports my claim, the experiments observed were done in vitro and in a
controlled environment. The next logical step would be to test TAM bound to gold nanoparticles
in vivo or on living subjects. Utilizing the method in vivo could have different results as it

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responds to constantly produced proteins rather than a predetermined amount placed in a
enclosed environment. The lack of trials on living subjects limits me to look at data from an
enclosed and controlled environment which may have different results from a living organisms
body.
Gold Nanocages as Photothermal Transducers for Cancer Treatment
Gold nanocages serve as a means to destroy cancerous cells through the process of
hyperthermia or exposing cells to heat extreme enough to cause denaturalization and kill the cell.
Gold nanocages are able to absorb light rather well and are able to convert light energy into
thermal or heat energy. PEGylated gold nanocages are administered to an organism intravenously
and are able to passively travel within the body to cancerous tumors. Once passively delivered to
the tumor, the nanocages either attach to the surface of the tumor or enter the tumor and attach to
the cancerous cells. The attached nanocages are then exposed to near-infrared light, which has a
wavelength between 600-900 nm, causing them to heat up and destroy cells around them.
Muscle, skin, and soft tissue has a low attenuation of light which allows near-infrared light to
penetrate deep within the body to reach the tumor and the nanocages. Trials of this treatment
have been done in vivo on living mice which all had cancerous tumors. The mice were separated
into two groups. The first group was administered 15nM PEGylated gold nanocages, and group
two received a simple injection of saline to act as a control group. The two groups of mice were
then subject to near-infrared light with a wavelength of 808nm directed towards their tumors.
After ten minutes of direct near-infrared light, the surface temperature of the control group's
tumor remained below 37 degrees Celsius, safe for soft tissue. The group of mice injected with
the gold nanocages saw a significantly different result. The surface temperature of the tissue rose
to 54 degrees Celsius in 2 minutes and remained about the same for the rest of the 10 minute

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period. After the 10 minute period of exposure to the near-infrared light, a F-FDG PET/CT scan
of the mice revealed significantly reduced metabolic activity within the tumors of the gold
nanocage mice compared to the control group of mice. The mice injected with gold nanocages
saw a 70% in metabolic activity in the tumors while the control group of mice saw nearly no
change. A histological examination also showed changes of coagulative necrosis in the tumor of
mice injected with gold nanocages, but this was absent in the mice exposed to light alone. The
experiment concludes that gold nanocages must be present for photothermal cancer treatment to
be successful.
The data collection was through experimental research and in vivo experiments where
live subjects, mice, were used to identify the effectiveness of near-infrared light and gold
nanocages on destroying tumors. The experiment concluded that the light itself had no effect on
the tumors, but near-infrared light combined with an injection of gold nanocages could destroy
tumors through hyperthermia. In addition to 70% reduced metabolic activity and signs of
coagulative necrosis, the journal identified that the nanocages had little to no effect on
surrounding healthy cells or tissue, and the destruction of the cells could be controlled by
reducing the light's intensity. The nanocage's ability to destroy tumors, target specific areas, and
avoid healthy cells implicates that gold particles are more effective in destroying cancerous cells.
Near-infrared light and gold nanocages are an effective method of destroying cancerous
cells, yet they avoid most healthy cells in the process. I would like to continue my research in the
direction of photothermal cancer treatment accompanied by gold nanoparticles or nanocages, but
few trials exist using photothermal cancer treatment. Also, traditional photothermal cancer
treatments don't exist without the use of gold nanocages or nanoparticles, so nothing exists for
me to compare the results to. I could compare results to radiation treatments which have a similar

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process. Although there is no baseline data on photothermal cancer treatment to which I can
compare the gold nanocage data, the near-infrared light and gold nanoparticle photothermal
method appears more effective and safer than traditional cancer treatments.
Gold Nanoparticles Enhance the Anti-Leukemia Action of a 6-Mercaptopurine
Chemotherapeutic Agent
6-Mercaptopurine (6-MP) is the most widely used medicine to treat leukemia which was
originally taken orally but now is administered intravenously. 6-MP has improved efficacy
through intravenous injection, but the medicine is quickly eliminated from the body and
bloodstream through the kidneys. To avoid removal from the bloodstream through kidneys, a
particle have a diameter of 3 nm and to achieve this the 6-MP particles are attached to gold
nanoparticles which carry the drugs past the kidneys. The increase in size allows the medicine
and gold nanoparticle to pass through the kidneys, but the particle cannot be too large otherwise
the reticular endothelial system (RES) may target and destroy the large gold particle. The
experiment, in vivo, set out to discover which delivery method is most effective in delivering 6MP and avoiding the renal system and the RES. The first trial determined which was most
effective in destroying cancerous cells: 6-MP alone, gold nanopaticles alone, or 6-MP and gold
nanoparticles. The gold particle with 6-MP attached proved to be most effective by a decent
margin on a crude graph. The microscopy of trial depicts a large destruction of cancerous cells.
The destruction by 6-MP and gold nanoparticles is much more significant than the control,
nanoparticles alone, and 6-MP alone. The second trial determined the effectiveness of increased
concentration of 6-MP particles or 6-MP attached to gold nanoparticles. The trial concluded that
as expected the higher concentration particles resulted in an across the board reduction in
cancerous cells. The trials also compared newly prepared 6-MP to gold nanoparticles which were

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for a year and concluded that the particles do not lose their potency while stored despite 6-MP's
qucik oxidation rate. In conclusion, the trials discovered that gold nanoparticles benefitted drug
delivery for a multitude of reasons. The gold nanoparticle allows 6-MP to bypass the renal
system, provides improved intracellular transportation, provides improved delivery to cell
interior and lysosomes, and prevents 6-MP from oxidizing and losing its potency over an
extended period of time. While there is no ideal particle size to completely avoid expulsion from
the blood stream, gold particle sizes are flexible and are able to be manipulated to reach a desired
time to circulate in the body.
The data analysis signifies that there are more benefits to gold nanoparticles than I
originally thought. I have compiled data simply showing that there radiation and chemotherapy
destroy more cancerous cells when paired with gold nanoparticles, but this article expands upon
more specific details like the ability to avoid the renal system and deliver the 6-MP particles to
the lysosomes. Although this journal provides smaller advantages and benefits of the gold
nanoparticle, it provides data that gold nanoparticles are capable of destroying more cancerous
cells than traditional chemotherapy alone. On a side by side comparison, 6-MP with gold
nanoparticles destroyed about 1x10^5 cells/ml more than 6-MP alone. The information gathered
from this journal implicates that traditional cancer treatments such as chemotherapy are more
effective when paired with gold nanoparticle. This journal supports my hypothesis as well.
This journal expanded upon the aspects and benefits that I should focus on while
examining gold nanoparticles. I should look at how the body reacts to the medicine and the
nanoparticles. I could also look at the interactions between the gold nanoparticles and the
chemotherapy drugs to determine whether they benefit each other like preventing oxidation and
improving time at which the medicine can be stored. As for limitations, I see no limits set by this

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journal. The journal has expanded upon more aspects of gold nanoparticle interactions with the
human body and other particles, and I should determine whether or not the interactions are
positive or negative. There are far more aspects that are waiting to be examined, and I have only
scratched the surface.
Gold Nanoparticles as Novel Agents for Cancer Therapy
The article provides a brief overview of the different methods and therapies the gold
nanoparticle can be used for. Chemotherapy, radiation, and imaging are described in brief, but
the article mostly focuses on the study of the radiation treatment accompanied by gold
nanoparticles. The study follows two sets of experiments, in vivo and in vitro. The in vitro
experiments tests the effects of radiation treatments with gold nanoparticles on cells outside of
the body. The experiments are commonly done in test tubes and Petri dishes to determine the
effectiveness of different sized nanoparticles and different amounts of radiation energy in
kilovolts and megavolts. The particles must be large enough to absorb energy to destroy
cancerous cells, but they have to be small enough to be well distributed within the tumor
otherwise cells on the surface of the tumor will only be destroyed. The most effective size in the
in vitro study was 15 nM with 1.2 MV of radiation and produced a destruction rate of 63.5% of
the cells within the enclosed environment. The second experiment, in vivo, was done in living
organisms namely mice. The test trials are needed in living organisms to ensure the process is
safe and to ensure the information translates from a controlled environment to a living organism.
The experiment consisted of three groups of mice which all had breast cancer. The mice were
either treated with radiation alone, radiation and gold nanoparticles, or gold nanoparticles alone.
The group treated with radiation alone experienced a growth delay in the cancerous tumors, but
the group treated with gold nanoparticles and radiation saw a significant reduction cancerous

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tumor growth when examined a month later. After a year, a 86% of the mice treated with the
combination of the two methods survived, but only 20% of the mice treated solely with radiation
survived. The mice treated with gold nanoparticles alone were all declared dead in less than a
year. In addition to a longer survival rate and improved tumor growth reduction, gold
nanoparticles were found in tumors farther from the capillaries and the bloodstream showing the
particles could deliver medicine to cells otherwise unaffected by traditional chemotherapy.
This study exemplifies the effectiveness of the gold nanoparticle accompanied with
radiation compared to either method used independently. The study also records the most
effective radiation energy and particle size for maximized tumor destruction. The increased
survival rate and length of survival show that pairing radiation with gold nanoparticles is more
effective in destroying cancerous cells than traditional methods alone. Though the experiment
does not directly record the percentage of cancerous cells destroyed within the mice or the
amount of healthy cells affected, the study does prove that gold nanoparticles accompanied by
radiation can have a significant effect on cancerous cells in living organisms. The study on living
mice shows that gold nanoparticles better target and damage cancerous cells stunting their
growth. The reduction of growth and improved survival rate implies the combination of the two
methods was successful in destroying a much larger quantity of cancerous cells than radiation
alone. My research question inquires about which method is most effective in destroying
cancerous cell, and the addition of this journal strengthens my hypothesis that traditional
methods accompanied by gold nanoparticles are more effective than traditional cancer treatment
methods alone.
Although the journal strengthens my hypothesis that the combinations of treatments is
more beneficial than radiation alone, it lacks precise numerical values of the percentage of which
the tumor reduced in size in living organisms and the effect the treatment has on human patients.

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The information is promising and hopeful, but trials on human patients would be more beneficial
and for the study. The largest limitation is the lack of clinical trials on human patients.