Eckert, 4:00
R01
THE USE OF NANOTECHNOLOGY IN TARGETED DRUG DELIVERY
THROUGH INHALATION FOR THE TREATMENT OF LUNG CANCER
Leonid Mirson (lem94@pitt.edu)
INTRODUCTION: AN OVERVIEW OF
ETHICS, EDUCATION,
NANOTECHNOLOGY, DRUG DELIVERY,
AND TREATMENT OF LUNG CANCER
medicine. Doing a lot of research and writing the paper
made me realize that while I have little interest in working in
the particular field of nanotechnology. While I think the
subject matter is fascinating, it is not something that I could
see myself doing for the rest of my life.
Why Investing in Nanotechnology for Drug Delivery is
Important
EDUCATION
I think that this assignment was really beneficial for me as
an engineering student. As mentioned earlier, it helped me
realize that I would not want to do this specific type of
research. But more than that, I think that writing is an
extremely important skill to have for engineers: “Engineers
will have to communicate clearly and persuasively in both
speaking and writing with other engineers and scientists,
systems analysts, accountants, and managers with and
without technical training, within their company and
affiliated with multinational parent, subsidiary, and client
companies, with regulatory agency personnel, and with the
general public” [1]. This is why a good engineering
curriculum will always have a significant writing
component. Good communication skills will be greatly
needed in all engineering disciplines in the future.
As a current undergraduate bioengineering student, my
belief is that nanotechnology in the medicine industry will
be a key innovation that will save millions of lives in the
future. It is of a particular interest to me because I plan on
going to medical school and perhaps someday using
nanotechnology as a resource to help patients.
Nanotechnology in medicine uses tiny particles (10^-9
meters in length) to help deliver drugs to places that need
them. One profound use for nanotechnology has been the
treatment of lung cancer, a notoriously difficult cancer to
treat using traditional chemotherapy. One of the most
fascinating uses for nanotechnology is the various kinds of
drug delivery that can be done using it. One of the most
promising methods, especially for the treatment of lung
cancer, is the inhalation of nanoparticles that carry
chemotherapeutic agents to lung cancer cells. This is why it
is absolutely essential to start investing more funding into
nanotechnology research, and, specifically, nanotechnologyinhalation research.
SPECIFICS OF NANOTECHNOLOGY
What is Nanotechnology
Ethical Issues
Nanotechnology by definition involves dealing with
particles that are very small (nanosized - about 10^-9 meters
in length). There are a myriad of different types of
nanomaterials used as drug delivery agents: “nano particles,
dendrimers, ceramic nanoparticles, chitosan nanoparticles,
liposomes, low-density lipoproteins, nanoemulsions, and
nanospheres” [2]. Each of these has its own benefits and
flaws, and thus researchers must decide which of them is
ideal for the treatment that is needed in a given case.
Molecules, such as nanoparticles, that approach the atomic
level often have different properties than their
macromolecular counterparts [3]. According to the “Nanotechnology and nano-toxicology” article, “gold is an inert
metal; nano-particles of gold les than 10 nm in diameter
burst into flames on contact with oxygen” [4]. Clearly there
are many dangers associated with using nanotechnology.
Engineer have an implicit ethical responsibility not to let
There are numerous ethical concerns regarding
nanotechnology and treatment of different cancers. As
someone who is looking to be an engineer and physician in
the future, the ethics of the ever-expanding fields of
nanotechnology and medicine is of great importance to me.
These ethical issues extend from the privacy problems
presented by nanotechnology, to a complete change of the
way we view human illness and disease.
Education
This project has been valuable to me in my engineering
education in that it forced me to take a look at what I am
truly interested in. Going into the paper, I knew that I was
interested in the many aspects of bioengineering and
University of Pittsburgh, Swanson School of Engineering
10/30/12
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Leonid Mirson
foreseeable harm come to clients, or, in this case, patients.
As stated in the National Society of Professional Engineers
Code of Ethics, “Engineers shall hold paramount the safety,
health, and welfare of the public” [5]. This means that before
proceeding to clinical trials, the various nanotechnologies
must be tested to be as safe as possible for patients due to the
various hazards involved with working with such new and
potentially deadly technologies. There are, however, many
boons that come with these innovations as well. Present day
chemotherapy using powerful drugs is the standard of care
for different cancers. However, this kind of therapy is often
nonspecific and thus can cause a wide range of side affects
as the drugs kill healthy cells as well malignant ones; what
nanotechnology allows medical professionals to achieve is a
much more precise way to eliminate cancer cells without
harming healthy ones [2]. It is clear, therefore, that
advancements in nanotechnology serve to better the
healthcare and the treatments of individuals throughout the
world.
My paper is focused on lung cancer specifically because it is
one of the cancers that shows great promise in treatment
with inhalation of nanomaterials. Lung cancer causes the
deaths of 23% of people living with cancer; it is rarely
operable and the 5 year survival rate with small cell lung
cancer is less than 10% [7]. Thus, any solution that helps to
alleviate this dramatic death rate is certainly worth
investigating.
Treatment
The idea of the inhalation treatment of nanomaterials is
highly innovative in that the particles get sent directly into
the lungs, bypassing travel through the bloodstream and
through other organs; therefore, no harm comes to other
cells in the body due to the toxic medication used to combat
the cancer cells. There are a number of factors that
researchers must consider with regards to treatment using
inhalation: how much oxygen to put in the mask, how much
carbon dioxide, the size of the dose, tumor size, method of
inhalation (ie. Inhaler, nebulizer, etc), liposome or
microparticles for the nanotechnology being used, and much
much more. It has been shown that adding 5-7% carbon
dioxide in the mixture greatly increases the effectiveness of
absorption of the drug by the lungs [7]. One of the greatest
things about drug delivery by inhalation is that there a
number of different methods to get the drug into your lungs.
However, using a nebulizer, a device that delivers
aerosolized droplets via a facemask can be the most
efficient, requiring “remarkably little patient coordination”
[7]. Liposomes were discussed earlier, but they are the
backbone of the nanotechnology used to provide treatment.
They are able to carry the needed medication inside them,
and they are able to bypass the body’s defense mechanism
thus reaching the cancer cells without being destroyed [7].
Microparticles are the next step beyond liposomes; they are
naturally occurring or synthetic polymers that are more
stable chemically than liposomes [7]. Therefore, they can
survive in a much more tougher and more likely to survive
in the body’s extreme environment. However, they also
serve a similar role to liposomes: encapsulating drugs that
can be delivered to specific cells. Many of these
nanoparticles have specific receptors so that they attach
themselves to specific cancer cells, without harming other
cells [7]. An example of the effectiveness of some of these
nanoparticles can be seen in the article regarding silica
nanoparticles’ toxicity in cancer cells: “In summary,
exposure to SiO2 nanoparticles results in dose dependent
cytotoxicity in cultural human bronchoalveolar carcinomaderived cells” [8]. This suggests that inhaled nanoparticles
can be deadly in the fight against lung cancer cells. As
shown in another article, the toxicity to the body is
significantly reduced using inhaled nanoparticles:
“Importantly, treatment of mice with either Pcpl or EpCAM
antibody solution caused 80% mortality and/or haemorrhage,
respectively, thus causing unacceptable toxicity. In contrast,
the survival of animals treated with either nano- or
Ethics of Nanotechnology and Manufacture
There are numerous ethical dilemmas when it comes to
nanotechnology and nanotechnology manufacture.
As
mentioned earlier, one of the risks associated with new
technology is the toxicity that the nanodrugs may have on
otherwise healthy cells. In addition to the nanoparticles’
toxicity on cells, one must also worry about other toxic
affects from the technology: “There are also valid concerns
over the disposal of nanowaste and environmental
contamination from the manufacture of nanomedical
devices” [6].
How Nanotechnology Work as a Means of Drug Delivery
A commonly used nanomaterial for drug transport is the
liposome. A liposome is made up of a phospholipid
membrane that has an inner core where drugs can be placed,
and these liposomes can be molded into various different
shapes and sizes that suit any particular purpose [2]. These
can be very useful because some drugs have poor solubility
otherwise, and the use of the liposomes allows them to be
several times more affective [3]. Liposomes are just one
example of nanotechnology being used for drug delivery.
While typically drug delivery involves intravenous injection
of nanomaterials containing the drug, one method is
becoming more and more prominent: drug delivery through
inhalation of nanomaterials.
NANOTECHNOLOGY AND TREATMENT
USING INHALATION IN LUNG CANCER
Background on Lung Cancer
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Leonid Mirson
immunonanoparticles was 60 and 70%, respectively” [9].
Pcpl and EpCAM are standard chemotherapy treatments that
do not utilize nanotechnology. Clearly, the medicines that
use nanotechnology are superior for the health of the
organism as compared with those that do not. Ultimately,
however, more research needs to be done. The positive
effects of inhaled nanomaterials are undeniable, yet the
negative effects are relatively unknown.
science, but also important communication skills that will
serve them for the rest of their engineering careers. I know
that this project has made me look hard at what I want to do,
and has taught me how to write in a scientific journal type
format. It has taught me that nanomedicine and
nanotechnology, especially when it comes to inhalation,
have an incredible potential to benefit the healthcare of our
society. The issue is without proper funding, many of these
potential benefits will never be discovered. As a future
bioengineer and physician, I cannot accept that our society
will forgo such amazing opportunities for the betterment of
itself simply because individuals either don’t know, or are
misinformed, about the field of nanotechnology and all of its
rewards. There is so much left to explore, and if one day
researchers find a cure or highly successful treatment for
lung cancer, a safe bet will be that it will be inhalation of
some sort of drug inside a nanomaterial. Despite this, one
must never be too hasty in experimenting with
nanotechnology. The ethical issues presented by these
innovations are many, and if handled improperly could be
the cause of innumerable societal problems and concerns.
Ranging from small to large, seemingly unimportant to
critical, and unavoidable to avoidable, as an engineering
student, I plan on learning about these early on and
informing as many people as I can. The reason I am writing
this article is to spread understanding of nanotechnology, its
potential problems, and its uses. Understanding begets
action, and action will create funding for the hundreds of
researchers in this exciting field.
Ethics of Treatment
One of the biggest ethical concerns lies in the patient privacy
issue that comes out of inhalation of nanoparticles. As stated
by Michael Berger, “Future nanotechnology-enabled,
implanted or swallowed diagnostic tools will make possible
the collection of an enormous amount of individual
cellular/subcellular level surveillance data of the human
body which then is remotely transmitted to a medical
database server to be analyzed and monitored by diagnostic
software” [6]. This means that the privacy of patients will be
increasingly put in danger. The amount of the information
collected will be voluminous and much work will have to be
done to keep patients’ information private. As long as that
data is stored properly and kept private, I think that it will
actually be a great innovation in the era of personal care.
Physicians and bioengineers will have so much information
about each individual patient at their disposal; each patient
will get the individualized care that they deserve. Another
ethical concern in the treatment of patients using
nanotechnology is that eventually engineers will have the
technology to detect any miniscule abnormality in a human
being [6]. This leads to the concern of what should be
treated and what should be left alone. It may lead to a
redefining of what we now call disease. Essentially, what is
and what isn’t disease? This is an important ethical question
that engineers will need to answer. My personal belief is that
when the time comes, we will have the availability of several
clinical trials to determine what is worth fixing and what
isn’t. Similar to how doctors choose not to treat small forms
of prostate cancer in older men (usually older men die of
other causes), engineers and physicians will have evidence
and experience available to deal with this issue. Also, there
will have to be new ethical guidelines and an ethical code
created specifically for any problems that may come up with
regards to treat or not to treat.
REFERENCES
[1] A. Rugarcia, R. Felder, D. Woods, J. Stice, et al. (2000).
“The future of engineering education.” Chem. Engr.
Education
(Online
article).
http://www4.ncsu.edu/unity/lockers/users/f/felder/public/Pap
ers/Quartet1.pdf
[2] R. Ranganathan, S. Madanmohan, A. Kasavan, et al.
(2012). “Nanomedicine: towards development of patientfriendly drug-delivery systems for oncological applications.”
International Journal of Nanomedicine. (Online article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292417/
[3] J. Sakamoto, A, van de Ven, B. Godin, et al. (2010)
“Enabling individualized therapy through nanotechnology.”
Pharmacol
Res.
(Online
Article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886806/
[4] R. Maynard. (2012). “Nano-technology and nanotoxicology.” Emerging Health Threads. (Online article).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365440/
[5] (2007). “Code of Ethics for Engineers.” National Society
of
Professional
Engineers.
(Online
article).
http://www.nspe.org/Ethics/CodeofEthics/index.html
[6] M. Berger. (2008). “Ethical aspects of nanotechnology in
medicine.”
Nanowork
LLC.
(Online
article).
http://www.nanowerk.com/spotlight/spotid=3938.php
CONCLUSION: EDUCATION AND THE
ETHICS AND SIGNIFICANCE OF
NANOMEDICINE AND INHALATION
DRUG DELIVERY FOR LUNG CANCER
TREATMENT
Education is quite obviously of great importance to
engineering students today. With a properly designed
curriculum, students can learn a great deal; not just math and
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Leonid Mirson
[7] P. Zarogoulidis, E. Chatzaki, K. Porpodis, et al. (2012).
“Inhaled chemotherapy in lung cancer: future concept of
nanomedicine.” International Journal of Nanomedicine.
(Online
article)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356182/
[8] W. Lin, Y. Huang, X Zhou, et al. (2006). “In vitro
toxicity of silica nanoparticles in human lung cancer cells.”
Toxicology and Applied Pharmocology. (Online article).
http://www.sciencedirect.com/science/article/pii/S0041008X
06003528
[9] K. N, N. T, L. F, et al. (2012). “Safety and Proof-ofConcept Efficacy of Inhaled Drug Loaded Nano- and
Immunonanoparticles in a c-Raf Transgenic Lung Cancer
Model.” Current Cancer Drug Targets. (Online article).
http://www.ncbi.nlm.nih.gov/pubmed/23030233
ACKNOWLEGDMENTS
I would like to thank my roommate, Joshua George, for help
in editing and suggesting ideas for my paper.
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