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Marvin Kajy
Jule Wallis
ENG 3010
07-19-2010.
Materials and Methods
Design
This experiment will employ a study group that suffers from lung cancer, which is
composed of 200 male participants female that represent the four major ethnicities in the United
States. These participants will undergo a new treatment procedure that employs the use of
nanoparticles as drug carriers that contain the anticancer drug Paraplatin®. The participants will
breathe in these nanoparticles via a medical ventilator and the progress of the lung cancer and the
work of the drug were monitored through an MRI machine.
Participants
Before starting this research, the experiment was reviewed by institutional review board
(IRB), which gave the approval to continue this study. The participants that were needed for this
study were selected from counties located in the state of Michigan. Specifically, the participants
were residents of Macomb, Oakland or Wayne County. The population that was studied
consisted of 200 people whose ethnicities fell under white, black, Asian/pacific islander or
Hispanic. The reason I used 200 people for this research study was because in science, the data is
regarded more valid when the researcher worked with a larger group rather than a smaller one.
These specific ethnic groups were chosen because they were the four major ethnic groups that
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made up the U.S. population. Furthermore, statistics had shown that lung cancer is most common
for people between the ages 55 and 85 and that is why all the participants that will be recruited
for this study will fall within this age group. Each ethnic group was considered a separate group
that consisted of 50 males. The reason I chose to focus on the male gender was because lung
cancer is more common in males and is the leading cancer killer in men in the U.S. By splitting
people in various groups, the researcher would be able to clearly see how people of different age
groups, backgrounds and gender will respond to this new treatment method.
The way people were recruited for this study was through advertisements placed in local
newspapers such as The Detroit News and the Detroit Free Press during the period of April1,
2009 to April 8, 2009. The ad contained information about the study performed, how long it
would run and what the requirements were to join the study. The ad also mentioned various
requirements that a person had to fulfill in order to be part of the study. An example of one
requirement was that a participant had to be diagnosed with lung cancer and s/he needed to
provide a written document from a physician to prove it. The types of lung cancer that was
accepted for this study was non-small cell lung cancer (NSCLC), being in stage I through stage
III. I believe that this new treatment technique will have the best results with NSCLC in stage I
through stage III. Another requirement was that the participant had to stay in the Detroit area
between the test period of May 1, 2009 to May 1, 2010. The reason I chose this particular time
length was because I really think that one year is needed in order to fully understand the effects
of the drug on both the human body and the cancer.
Once 200 participants were obtained for the study, individual appointments were made
with each person that lasted 30 minutes. During these appointments, medical records of the
participant were collected and the details of the study were explained. To illustrate, the
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participant was explained the purpose of this study, how it will be performed along with the
benefits that s/he will receive throughout the test period. The experiment required the
participants to put in a lot of time and effort into this research and that is why they received
benefits such as a $500.00 compensation for each month along with health insurance coverage
by Blue Cross Blue Shield of Michigan. If the participant agreed with the experiment, then s/he
signed a consent form that stated that s/he is participating on a voluntary basis and s/he legally
authorized the research team to collect any medical data necessary for the experiment.
In the end, I do think that the benefits of this study will outweigh the risks. Lung cancer
is the cancer type that is currently claiming the most lives in males. Current treatment methods
are not effective because they cause a lot of dangerous side effects and in some cases they only
treat the symptoms and not the actual illness. A new treatment technique is needed to effectively
treat this disease and I believe that a drug delivery system powered nanoparticles will finally
provide an effective cure.
Materials/Stimuli
The nanoparticles were synthesized by using a process called reverse micelle. This
process called for a nanoparticle that consisted of a porous gold outer layer, with a hollow iron
core. The hollow cavity in the interior of the nanoparticles will be able to hold various types of
anticancer drugs, for my test purposes I used Paraplatin® supplied by American Custom
Chemicals Corporation, which is one of the most widely used anticancer drug. For this research,
I choose to synthesize the nanoparticles model that employed the reverse micelles method was
because earlier research performed by another research group has shown that nanoparticles
synthesized from this process had unique properties that were beneficial for both the researcher
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and the participants. To illustrate, this design gave the scientist control about the behavior of the
drug once it was inside the body and the metals used are not toxic to the patient.
The apparatus that was used to administer the drug was a Galileo Medical Ventilator by
Hamilton medical. If a medication is administered via an inhaler, then it will enter the body
through the respiratory system and ultimately reach the lungs, which is where the cancer
originated. I think that if the medication is administered directly to the source of illness, then the
overall treatment method will be more effective and it will most likely speed up the treatment
method.
Procedure
The first task of the experiment was to make the nanoparticles that will act as the drug
carriers for the anticancer drug, which was done by using reverse micelles. The nanoparticles
were formed with about a 6 nm diameter gold core, 1 nm iron interlayer and 2 nm gold shells.
These nanoparticles were then attached to a lung cancer targeting peptide and coated with super
paramagnetic iron oxide (SPIO) and doxorubicin (Doxo) for MR imaging and therapeutic
delivery. Once 10.00 grams of the final product was made, High-performance liquid
chromatography (HPLC) was used to assess the binding between the nanoparticle and the
peptide. 5.00 g was dissolved in 100 ml distilled water supplied by Purefact Inc. This solution
was put into a machine that will emit these nanoparticles as a fine mist that a subject can breathe
through a breathing tube.
Each participant was instructed to undergo 12 clinical examinations over a period of six
months. Each clinical examination included a short interview in which the participant was asked
whether s/he was suffering from any pain throughout the body. Afterwards, a full body MRI scan
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was taken using Philips Achieva 3.0T X-Series MRI machine to see how far the cancer has
spread. Then, the participant was told to go to another room were s/he would get administered
the medication. The participant was told to sit on a chair and to breathe through a breathing tube
for a period of three hours. The tube was connected to a machine that emitted the nanoparticles
in the form of a vapor that a person can breathe. After the medication was administered, a MPG5
Magnetic Pulse Generator by SOTA Technologies was used to emit a magnetic signal that will
instruct the nanoparticles to detect tumor cells and to deliver the medications only to the tumor
cells. This was done by putting the device on a patient’s chest and turning it one for five minutes.
Finally, at the end of each visit, another MRI scan was taken for analysis and the patient was told
to come back in two weeks.
This was done every two weeks for a period of six months. The first few weeks, the lungs
will be examined for any traces of cancer by using the MRI scans. If the lungs still contained
tumor cells, then the nanoparticles would remain and do their work in the lungs. However, if the
lungs were determined to be cancer free, then the nanoparticles will receive a second magnetic
signal that will instruct them to move to the rest of the body via the circulatory and the lymphatic
systems, where they will search for more cancer cells and deliver the drugs. Afterwards, every
two weeks, full body scans will be run on the patient to determine how much cancer is in the
body. Finally, if the patient was determined to be cancer free, then a third signal will instruct the
nanoparticles to break down, which allowed them to be degraded by various enzymes already
present in the body.
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Results
Table 1
Properties of the Nanoparticles Synthesized
SPIO Loading
micelles
LCP20MFM
lung cancer
targeting peptide
RGDLATLRQL
surface density
(%)a
size
(nm)b
21
46
DOXO Loading
LC (%)c LE (%)d
11.6
67
LC (%)c
LE (%)d
5.02
65
a) Molar percentage of Mal-PEG-PLA copolymers conjugated with the lung cancer targeting
peptide (HPLC shows a binding efficiency of 95% or more).
b) Diameter of the nanoparticle
c ) Loading content (LC) was calculated as the weight percentage of SPIO or Doxo over the total
micelle weight.
d ) Loading efficiency (LE) was calculated as the percentage of loaded SPIO or Doxo over the
original feeding amount.
Table 2
Ethnicity
Amount of people
determined to be
cancer free
Amount of people that
only experienced a
reduction in tumor size
Amount of people
that showed no effect
to the new drug
Observed
side
effectse
White
45
3
1
Black
47
3
0
Asian/Pacific islander
46
2
2
Hispanic.
45
0
5
Relatively
minor
Relatively
minor
Relatively
minor
Relatively
minor
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e) The side effects that many participants experienced were not severe in comparison with
current treatment methods (surgery, radiotherapy, chemotherapy) and lasted only for several
hours. The observed side effects included headache, dizziness, fatigue, vomiting upset stomach,
dry or sore throat and difficulty breathing.
Discussion
The purpose of this research study was to see whether a new nanoparticle based drug
delivery system, will provide an effective cure for lung cancer. There were two characteristics
that were heavily empathized during this experiment and that is that this new drug had to be
effective and it had to be so without producing significant side effects. Based on the results
gathered, one can see that patients with stage I through stage III lung cancer revealed an
excellent response rate to this new drug delivery system. After one year has elapsed, 90% or
more of the people in each ethic group were determined to be cancer free. Additionally, there
were some that only saw a reduction in size of the tumor. A possible explanation of why these
participants were not cancer free can be that the treatment period of one year might not have
been long enough and the patient only required an extend treatment period. Another possible
explanation can be that the patient’s body did not respond well to the anticancer drug
Paraplatin® and s/he requires a different medication. This problem is easily fixed by inserting a
new medicine into the nanoparticle’s hollow core and following the same procedure. All these
results indicate that this new treatment method worked very well for our study group and it is
ready to be further tested by other research teams with their own unique participants.
Although the majority of the study group responded well to the new medication, there
were some people that experienced relatively no effect in tumor size. As mentioned earlier, a
possible explanation for this is that the patient’s body did not respond well to the anticancer drug
and s/he just requires change in the anticancer drug. The patients did experience some relatively
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mild side effects in comparison with existing treatment methods. Fortunately, they were not One
can see that the results obtained open up many new and exciting opportunities of
377 5570
Transmission Electron Microscopy Study of Gold-Coated Iron
Core-Shell and Au/Fe/Au Onion-Like Nanoparticles Synthesized
Using Reverse Micelles
Synthesis and agglomeration of gold
nanoparticles in reverse micelles