Bursic, 2:00

R08

NANOPARTICLE TARGETING SYSTEMS FOR CANCER THERAPY

Sean Klevens (skk24@pitt.edu)

INTRODUCTION: CANCER TARGETING

THE PROBLEM
Current cancer treatments usually involve intrusive
processes including the use of catheters (tubes that are
inserted into a body cavity) to administer chemotherapy,
surgery to remove the tumor that has hopefully been shrunk
by the chemotherapy, followed by more chemotherapy and
radiation [1]. The purpose of chemotherapy and radiation is
to kill the tumor cells which are more susceptible to these
methods than healthy cells are. This is due to the rapid
growth rate of cancerous cells [1]. Research efforts to
improve chemotherapy over the past decade have led to a
26% increase in the survival rate of cancer patients, but there
is still a need for improvement [2]. Current exploration has
led to an interest in both nanoparticles that target the cancer
cells and ones that target the blood vessels fueling tumor
growth. The effectiveness of a treatment is directly related
to the treatments ability to target and to kill the cancer cells
while affecting as few healthy cells as possible. The degree
of change in a patients quality of life and life expectancy is
dependent to this targeting ability. A treatment with low
targeting ability will cause more damage to healthy cells
thus reducing a patients quality of life and life expectancy,
so more accurate methods of targeting are vital [3]. The
majority of current cancer patients only get the most basic
targeting which is simply the inherent tendency of the
chemotherapy to affect the cancer cells more intensely than
healthy cells. Sometimes the side effects of these intense
drugs are so severe that the patient must discontinue therapy
before the drugs can eliminate or reduce the tumor(s), and
not all treatments are effective in killing the cancer before
the cancer kills the patient. For these reasons, further
research into the nanoparticles which can deliver treatment
more directly is imperative to the health and survival of
cancer patients. However, it is of the utmost importance that
any research done is conducted in a manner consistent with
all ethical codes applicable to the project, which is
something that should be emphasized in engineering
training.

UNDERSTANDING TUMORS
Tumors form when genetic mutations occur causing the
genes which regulate cell growth to be altered [2].
A
cancerous cell surrounded by healthy tissue will replicate at
a higher rate than the other cells, which puts a strain on the
nutrient supply. Once a small tumor mass has formed, the
healthy tissue will not be able to compete with the rapidly

University of Pittsburgh, Swanson School of Engineering 1

October 30, 2012

reproducing cancer cells for the nutrients from the blood

stream [1]. Tumor cells will displace healthy cells until
the tumor reaches a maximum size. This maximum size has
to do with the amount of nutrients the cancer cells are
receiving [3]. The cells toward the center of the cancerous
mass rely on diffusion from the outer cells so, when there
are not enough nutrients, they die. Since the cancer cells
continue reproducing without regard to the insufficient
nutrient supply, the cells towards the center of the mass
essentially starve [1]. Therefore, the maximum size is the
size at which the cancer cells are dying at the same rate they
are reproducing. This will keep the tumor from growing
larger until the tumor recruits the formation of blood vessels
to provide the nutrients necessary to fuel its continued
expansion (which can take years) [1]. Researchers do not
yet know what initiates the rerouting of blood vessels, but
the factors involved present new (and most likely highly
effective) targets for nanoparticles to seek out.

UNDERSTANDING NANOPARTICLES
Nanoparticles are generally considered to be particles
with dimensions in the 1-100 nanometer range [4]. In
medicine, they are precisely engineered so as to be attracted
to diseased cells. This is through the careful combination of
different elements and drugs on the surface of the particle
[4]. When nanoparticles are injected into the human body,
they will usually be taken up by the liver, spleen, and the
lymphatic system (these are the regions with the greatest
immune response) [4]. The body views them as intruders
and does its best to destroy them. However, coating them
with a substance called poly, for example, allows for 5-10%
of the particles to still be circulating in the bloodstream eight
hours after injection [3]. Poly disguises the particles, and
greatly reduces the rate at which the body destroys them.
Particles with a longer circulation time have a greater ability
to target the site of interest. This means that there will be
less damage to the healthy cells of cancer patients by the
harsh drugs, reducing the severity of their side-effects and
also increasing the odds that the medication will make a
difference in reducing tumor size [3].

TUMOR-SPECIFIC TARGETING
Although there are a number of different targeting
methods for nanoparticle delivery (all of which have specific
benefits and should be researched further), the most
promising one as of today is called tumor-specific targeting
[3]. This approach uses nanoparticles coated in drugs that
will not activate until they reach the tumor. The surfaces of

Sean Klevens

cancer cells often have different chemical compositions than

the healthy cells, so using a combination of drugs that
remain inactive until exposed to the chemicals found on the
surface of the cancer cells would be ideal [3]. Doctors
would just have to make sure that those chemicals that are
on the surface of the cancer cells are not present (in large
quantities) anywhere else in the body or else the drugs could
be delivered to the wrong location.

GENERAL ENGINEERING ETHICS AND

NANOPARTICLE TARGETING SYSTEM
DEVELOPMENT
Due to the importance of research into nanoparticle
targeting systems, and to the widespread effect this
technology will have on the world, engineers must at all
times adhere to the National Society of Professional
Engineers code of ethics.
The NSPE states that
Engineering is an important and learned profession. As
members of this profession, engineers are expected to
exhibit the highest standards of honesty and integrity.
Engineering has a direct and vital impact on the quality of
life for all people. Accordingly, the services provided by
engineers require honesty, impartiality, fairness, and equity,
and must be dedicated to the protection of the public health,
safety, and welfare [6]. To uphold this ideal, the NSPE
created six fundamental canons that all engineers must
follow in the fulfillment of their professional duties. The
ones most applicable to this specific area of research are the
first and fifth canons. The first states that all engineers must
Hold paramount the safety, health, and welfare of the
public [6]. This means that developers cannot cut corners
during the drug creation and testing processes. It is their
responsibility to make sure that everything they release to
the public for clinical use is completely safe and effective
beyond all reasonable doubt. Failure to do this could result
in harm to the drug users. The fifth canon states that
engineers must avoid deceptive acts [6]. Engineers
working on nanoparticle targeting must not issue
exaggerated statements regarding the success of their
systems, nor bend the results of their trials to make their
research appear more promising. Attempts to personally
profit from warped results can cause imperfect methods of
drug delivery to move to stages of development that they are
not ready for (i.e. clinical trials) which is not only dangerous
but can also put the study off course.

THE IMPORTANCE
This is truly a matter worth pursuing. Over 1.5 million
new cases of cancer are projected to occur in the United
States alone this year, and over half a million people will die
from it [5]. One in four US deaths is due to cancer, and
these nanoparticle targeting systems have the potential to
reduce this disturbing number [5]. They also have the
promise of improving the quality of life for the patients.
Many undergoing chemotherapy experience symptoms so
severe that they cannot continue treatment (and in some
cases this is a life or death matter). Chemotherapy can
depress the immune system, which can result in potentially
fatal infections. In serious cases, treatment is stopped in
order to allow the immune system to recover. It can also
cause serious nausea, vomiting, and diarrhea which often
leads to dehydration and malnutrition [1]. Through the
improvement of nanoparticle targeting systems, the drugs
could be delivered more directly to the tumor which would
greatly reduce the side-effects and symptoms of
chemotherapy. The lives of millions of cancer patients
around the world would be saved and even more would at
least be improved and elongated.

MY PERSONAL INTEREST
Practically everyone has a family member or friend
afflicted with cancer. A number of people close to me have
passed away over the years due to this terrible disease, and
almost 17,000 new families each day have to deal with the
loss of a family member because of it [5]. Ever since career
day my senior year of high school (after a presentation about
the application of nanoparticles in medicine given by a
biomedical engineer), I knew I wanted to pursue this topic
further. Nanoparticle targeting is a revolutionary technology
with the potential to literally change the world. Getting
involved in the improvement of the targeting systems would
be both rewarding and exciting. Knowing that I am working
to make a difference in the lives of millions of people would
keep me motivated, and the thought of getting closer and
closer each day to finding an effective drug delivery method
would be genuinely thrilling.

BIOMEDICAL ENGINEERING ETHICS

Engineers working on nanoparticle targeting system
development must be sure to adhere to the Biomedical
Engineering Societys code of ethics in addition to the
general code of ethics seeing as though biomedical
engineering is a pivotal part of this research field. The code
states that public health and welfare are paramount
considerations in each [area of biomedical engineering], and
biomedical engineers must uphold those principles of ethical
conductin all professional practice, research, patient care,
and training [7]. Specifically, engineers working with
nanoparticle targeting for cancer therapy must consider the
larger consequences of their work in regard tothe delivery
of health care [7]. This essentially means that they must
accept nothing short of perfection when it comes to treating
patients with the drugs they developed. Giving an imperfect
2

Sean Klevens

drug to a patient in a trial has the potential to cause serious

harm to someone who is already suffering. The engineers
must fully understand every aspect and possible outcomes of
their research decisions. Another important aspect of the
BMES code of ethics that pertains to this field of research is
that biomedical engineers entrusted with the responsibility of
training others shall honor the responsibility not only to
train biomedical engineering students in proper professional
conductbut also to model such conduct before them [7].
The training of new engineers to work on this significant
task is paramount to its ultimate success. Having a greater
number of researchers will accelerate the rate at which the
technology is perfected. However, the engineers responsible
for passing on their knowledge must do so in a manner
consistent with the code. They must themselves be good
role models by following all regulations set down for them
and by demonstrating proper techniques and methods. They
also must keep their training methods and content free from
inappropriate influences and special interests.

patients worldwide, and I pray that it will be perfected and

become available in the near future.

REFERENCES
[1] (2011). Understanding Cancer. Chemotherapy.com.
(Online
Article).
http://www.chemotherapy.com/understanding_cancer/unders
tanding_cancer.html
[2]
(2011).
Glossary
of
Cancer
Terms.
Chemotherapy.com.
(Webpage).
http://www.chemotherapy.com/glossary/terms.html#T
[3] K. Jaid. (2009). Targeted Drug Delivery for Cancer.
Technology in Cancer Research and Treatment. (Online
Article).
http://www.tcrt.org/OpenAccess/Ed_TCRT_4_4_311.pdf
[4]
T. Cedervall.
(2009).
Understanding the
Nanoparticle.
PNAS.
(Online
Article).
http://www.pnas.org/content/104/7/2050
[5] R. Siegel. (2012). Cancer Statistics, 2012. Wiley
Online
Library.
(Online
Article).
http://onlinelibrary.wiley.com/doi/10.3322/caac.20138/pdf
[6] (2012). NSPE Code of Ethics for Engineers.
NSPE.org.
(Online
Article).
http://www.nspe.org/Ethics/CodeofEthics/index.html
[7] (2009). Biomedical Engineering Society Code of
Ethics.
BMES.org.
(Online
Article).
http://www.bmes.org/aws/BMES/asset_manager/get_file/19
110?ver=3480
[8] M. Davis. (2011).
Teaching Ethics Across the
Engineering Curriculum.
OnlineEthics.org.
(Online
Article).
http://www.onlineethics.org/Education/instructessays/curric
ulum.aspx#why

EDUCATIONAL VALUE OF TEACHING

ENGINEERING ETHICS
Because of the importance of proper ethical conduct in
the field of engineering, ethics is certainly a valuable topic to
cover in any engineering program. Although many of the
points made in the codes are simply common sense, there are
other less obvious canons that should be learned [8]. For
example, I personally was unaware of the specific guidelines
drawn out for engineer mentors, and this could have affected
my teaching methods if I ever become a mentor to younger
engineers. If students are never taught the ethical codes,
they will be at risk of violating them albeit unknowingly. As
such, universities should take initiative to add ethics to their
engineering curriculum.

CONCLUSION: HOPE FOR THE

FUTURE

ACKNOWLEDGEMENTS
I would like to thank the biomedical engineer who came
to my physics class one day during my senior year of high
school to talk about the application of nanoparticles in
medicine. He was the one who first introduced me to this
interesting subject. I would also like to thank the Forbes
Hall Floor 3 crew who helped me with my formatting and
who proofread my paper.

Research activity aimed towards developing and

improving nanoparticle targeting systems has expanded
tremendously in the past years with new ways of delivering
the drugs to tumors as well as new types of drugs. Cancer
drug delivery is no longer simply wrapping the drug in a
new formulation [3]. However, despite the great strides we
have made, there is a great deal more that can be done to
treat and perhaps prevent the advance of cancer. Through
our current knowledge of tumors and nanoparticles we have
developed many methods with great potential. Now, we
must refine them and make them safe and consistent so that
they can be practically applied in patient care (whilst
conforming to all applicable codes of ethics). This emerging
technology is truly a shining beacon of hope for cancer