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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 treatment’s ability to target and to kill the cancer cells
while affecting as few healthy cells as possible. The degree
of change in a patient’s 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 patient’s 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

and biomedical engineers must uphold those principles of ethical conduct…in all professional practice. Chemotherapy can depress the immune system. the services provided by engineers require honesty. This essentially means that they must accept nothing short of perfection when it comes to treating patients with the drugs they developed. safety.000 new families each day have to deal with the loss of a family member because of it [5]. clinical trials) which is not only dangerous but can also put the study off course. One in four US deaths is due to cancer. To uphold this ideal. The lives of millions of cancer patients around the world would be saved and even more would at least be improved and elongated. This means that developers cannot cut corners during the drug creation and testing processes. and over half a million people will die from it [5]. The code states that “public health and welfare are paramount considerations in each [area of biomedical engineering]. and the thought of getting closer and closer each day to finding an effective drug delivery method would be genuinely thrilling. 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. Engineering has a direct and vital impact on the quality of life for all people.e. health. nor bend the results of their trials to make their research appear more promising. BIOMEDICAL ENGINEERING ETHICS Engineers working on nanoparticle targeting system development must be sure to adhere to the Biomedical Engineering Society’s code of ethics in addition to the general code of ethics seeing as though biomedical engineering is a pivotal part of this research field. Accordingly. THE IMPORTANCE This is truly a matter worth pursuing. Getting involved in the improvement of the targeting systems would be both rewarding and exciting. engineers must at all times adhere to the National Society of Professional Engineers’ code of ethics. Specifically. 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). A number of people close to me have passed away over the years due to this terrible disease. GENERAL ENGINEERING ETHICS AND NANOPARTICLE TARGETING SYSTEM DEVELOPMENT Due to the importance of research into nanoparticle targeting systems. I knew I wanted to pursue this topic further. the drugs could be delivered more directly to the tumor which would greatly reduce the side-effects and symptoms of chemotherapy. impartiality. engineers working with nanoparticle targeting for cancer therapy must “consider the larger consequences of their work in regard to…the delivery of health care” [7]. The ones most applicable to this specific area of research are the first and fifth canons. the NSPE created six fundamental canons that all engineers must follow in the fulfillment of their professional duties. and equity. fairness. treatment is stopped in order to allow the immune system to recover. and welfare” [6]. vomiting. 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]. The first states that all engineers must “Hold paramount the safety. which can result in potentially fatal infections. Through the improvement of nanoparticle targeting systems. As members of this profession. and training” [7]. In serious cases. Engineers working on nanoparticle targeting must not issue exaggerated statements regarding the success of their systems. and these nanoparticle targeting systems have the potential to reduce this disturbing number [5]. MY PERSONAL INTEREST Practically everyone has a family member or friend afflicted with cancer. research. 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. engineers are expected to exhibit the highest standards of honesty and integrity. and diarrhea which often leads to dehydration and malnutrition [1]. The NSPE states that “Engineering is an important and learned profession. patient care. and must be dedicated to the protection of the public health. Over 1.Sean Klevens cancer cells often have different chemical compositions than the healthy cells. Knowing that I am working to make a difference in the lives of millions of people would keep me motivated. Nanoparticle targeting is a revolutionary technology with the potential to literally change the world. Giving an imperfect 2 . The fifth canon states that engineers must “avoid deceptive acts” [6]. 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). and welfare of the public” [6]. and to the widespread effect this technology will have on the world. 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.5 million new cases of cancer are projected to occur in the United States alone this year. Failure to do this could result in harm to the drug users. and almost 17. It can also cause serious nausea.

org/Ethics/CodeofEthics/index. http://www. “Teaching Ethics Across the Engineering Curriculum.com. “Understanding Cancer. there is a great deal more that can be done to treat and perhaps prevent the advance of cancer.org. 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 conduct…but also to model such conduct before them” [7]. despite the great strides we have made. I would also like to thank the Forbes Hall Floor 3 crew who helped me with my formatting and who proofread my paper.org. (Online Article). and this could have affected my teaching methods if I ever become a mentor to younger engineers. http://www.org/Education/instructessays/curric ulum.” NSPE. Siegel. universities should take initiative to add ethics to their engineering curriculum. 2012. 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.com/understanding_cancer/unders tanding_cancer. “NSPE Code of Ethics for Engineers. Having a greater number of researchers will accelerate the rate at which the technology is perfected.nspe. the engineers responsible for passing on their knowledge must do so in a manner consistent with the code. (2009). http://www. However.” OnlineEthics. “Biomedical Engineering Society Code of Ethics. 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. Although many of the points made in the codes are simply common sense. Through our current knowledge of tumors and nanoparticles we have developed many methods with great potential.chemotherapy. As such.” Technology in Cancer Research and Treatment.com.html#T [3] K. “Cancer drug delivery is no longer simply wrapping the drug in a new formulation” [3]. (Online Article).Sean Klevens drug to a patient in a trial has the potential to cause serious harm to someone who is already suffering. REFERENCES [1] (2011).pnas. “Cancer Statistics. there are other less obvious canons that should be learned [8].20138/pdf [6] (2012). This emerging technology is truly a shining beacon of hope for cancer 3 . For example.org/aws/BMES/asset_manager/get_file/19 110?ver=3480 [8] M. (Online Article).html [2] (2011). (2012).org/content/104/7/2050 [5] R.pdf [4] T. (Online Article). The training of new engineers to work on this significant task is paramount to its ultimate success. However.tcrt.wiley. The engineers must fully understand every aspect and possible outcomes of their research decisions.html [7] (2009). Jaid.org. “Targeted Drug Delivery for Cancer. Cedervall. I personally was unaware of the specific guidelines drawn out for engineer mentors. He was the one who first introduced me to this interesting subject. they will be at risk of violating them albeit unknowingly.com/doi/10. (2009).com/glossary/terms. http://www. (2011). They must themselves be good role models by following all regulations set down for them and by demonstrating proper techniques and methods.bmes. patients worldwide.” Chemotherapy. (Online Article). Davis. http://onlinelibrary. and I pray that it will be perfected and become available in the near future.” PNAS.” BMES.onlineethics. (Online Article). Now.aspx#why EDUCATIONAL VALUE OF TEACHING ENGINEERING ETHICS Because of the importance of proper ethical conduct in the field of engineering. “Understanding the Nanoparticle.” Chemotherapy.chemotherapy. http://www. (Webpage). http://www. (Online Article).” Wiley Online Library.3322/caac. 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). http://www. “Glossary of Cancer Terms. ethics is certainly a valuable topic to cover in any engineering program.org/OpenAccess/Ed_TCRT_4_4_311. If students are never taught the ethical codes. They also must keep their training methods and content free from inappropriate influences and special interests.