Download photodynamic therapy: soon to be the first

B13
198
Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University
of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on
publicly available information and may not be provide complete analyses of all relevant data. If this paper is used for any
purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at
the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
PHOTODYNAMIC THERAPY: A NEW METHOD TO TREAT SKIN CANCER WITH
MINIMAL DRUG USE AND SIDE EFFECTS
Austin Blair, [email protected], Budny 10:00, Gabrielle Robinson, [email protected], Budny 10:00
Abstract- Millions of people are diagnosed with skin
cancer each year in the United States, which in some cases
has the potential to be fatal. Photodynamic therapy was
first developed over 30 years ago for various diseases but
is just now being applied to skin cancer treatment. It has
recently gained recognition as a way to eliminate the need
for invasive surgeries and reduce side effects making for a
smoother and safer recovery. Over the past few years it has
become a treatment option that is offered at the nation’s
top oncology centers, such as the Roswell Park Cancer
Institute in Buffalo, New York. Photodynamic therapy
allows for pinpoint delivery and activation of a drug using
photosynthesizing agents made of a drug molecule weakly
bonded to a carrier molecule. The ability for a drug to only
be activated in the necessary region means the chance of
this drug harming other parts of the body along its travels
is very slim. Traditional chemo treatments involve active
drugs that circulate throughout the body and not only
damage the cancer cells but damage healthy cells as well.
This can cause numerous side effects, such as loss of hair
or fatigue. A photodynamic drug can circulate safely
through the body while remaining inactive; it is only
activated when exposed to long wavelength light in the
region where the light is being projected. The advantages
of photodynamic therapy are many and will have profound
effects on the millions of those who suffer from skin cancer.
been invented. As technology and the understanding of
biological and chemical processes has progressed,
photodynamic therapy has been made more efficient, less
expensive, and a safer form of skin cancer treatment.
Photodynamic therapy is now a suggested treatment option
for many patients with skin cancer and is growing within
the oncology field.
A Basic Overview
Skin cancer affects an extremely large portion of the
American population. Over five million Americans are
diagnosed with skin cancer each year, and about one in five
will develop some form throughout their lifetime [2].
Photodynamic therapy’s biggest impact will be in
melanoma treatment perhaps, as it is the deadliest form of
skin cancer. Only a small fraction of skin cancer patients
are diagnosed with melanoma, however, it is the leading
cause of death among those who have some form of skin
cancer. It is estimated that about 75,000 adults in the
United States are diagnosed with melanoma each year and
over 10,000 of those will lose their life to the disease [3].
Traditional treatments can be taxing on the patient and
have unwanted and harmful side, which is why
photodynamic therapy can help so many. PTD can reduce
the need for potentially harmful treatments, while having
few to no side effects, as well as being a much faster drug
delivery system.
Photodynamic therapy combines aspects from both
chemical and bio-engineering to treat melanoma skin
cancer. PTD is a process in which long wavelength light
activates a drug to effectively kill cancer cells. A
photosensitizing agent is injected into the blood stream and
is absorbed by the red blood cells, it circulates throughout
the body and remains inactive until exposed to light. The
photosensitizing agent is a compound made of drug
molecules weakly bonded to a carrier molecule,
traditionally a vitamin or protein. However, recent research
has indicated that certain nanoparticles may act as more
efficient carriers which will be discussed later in the
analysis of PTD. In treatment for skin cancer, the tumor or
targeted area is exposed to long wavelength light after the
drug circulates through the body for three days [4]. Once
the afflicted area is exposed to light, the photodynamic
Key Words - Photodynamic Therapy (PDT),
Photosensitizing Agent/Photosensitizer, Cytotoxic free
radicals, Singlet Oxygen, Superoxide
BASICS OF PHOTODYNAMIC THERAPY
A Brief History
Photodynamic therapy (PTD) was hypothesized as a
viable treatment for melanoma and other skin cancer over
thirty years ago and the first successful use of light and
chemical to kill a microbe was observed over one hundred
years ago by German medical student, Oscar Raab [1].
However photodynamic therapy is only now becoming a
widely-used treatment for skin cancer. In recent years
photosensitizing drugs have been improved, and the
development of less expensive means of light delivery have
University of Pittsburgh Swanson School of Engineering
03.31.2017
1
Austin Blair
Gabrielle Robinson
drug separates from the carrier and becomes “active.” The
light from the laser produces enough energy to break the
bonds of the photosensitizing agent but not enough to cause
a lot of harm to healthy cells within the vicinity. Once the
bond is broken, the drug attacks and destroys the cancer
cells, as well as the capillaries that feed it [5].
The ability for the drug to only be activated at the site
of the tumor means that there are no side effects elsewhere
in the body because the drug is dormant until activated,
unlike traditional chemotherapy drugs [6]. PTD is also a
faster means of treatment because it could take as few as
one successful treatment to destroy the entire tumor. The
use of photodynamic therapy will continue to grow in not
only skin cancer treatment, but other disease treatments, as
the process is further researched and perfected.
different versions of oxygen because the photon accepted
by the photosensitizer is used differently.
Photosensitizers come in many shapes and sizes, made
of different chemicals and compounds. However, effective
or “ideal” photosensitizers all share the same qualities.
They are a single pure substance that is stable at room
temperature. Photosensitizers are minimally toxic without
light and only become cytotoxic in the presence of like
between 700 nanometers and 850 nanometers. They
produce a singlet oxygen or radical superoxide and have
optimal electromagnetic absorption. Another characteristic
of an ideal photosensitizer is effective they are at
penetrating the tumor. The photosensitizers will
accumulate within the tumor and for optimal results they
accumulate at a subcellular level within organelles of the
individual cancer cells which delivers an apoptotic cell
death rather than a necrotic cell death which is much a
much safer way to destroy the cells [7].
In the first type of photosensitization reaction, a
photosensitizer is excited when exposed to electromagnetic
radiation because it absorbs a photon from the light. When
the photosensitizer is excited it undergoes an internal
reaction that leads to chemical changes to the molecule.
The addition of the photon causes a “one-electron transfer
reaction” where a radical ion is produced in both the
sensitizer and substrate, or carrier molecule. Usually an
electron is transferred from the substrate to the
photosensitizer to produce substrate radical cation and a
photosensitizer radical anion. These free radicals further
react with the oxygen in the blood to produce a superoxide
radical anion which is used in cancer cell treatment. The
second reaction follows the same steps as the first type. A
photosensitizer is excited when exposed to electromagnetic
radiation however, there is no electron transfer between a
substrate
and
the
photosensitizer.
Once
the
photosensitizing agent is excited it transfers an electron to
a ground state oxygen molecule, which turns into an
excited singlet oxygen [8]. These singlet oxygens are used
to kill cancer cells as well.
In both reactions, the photosensitizing agent is
reproduced as a final product which allows the reaction to
take place again [8]. This aspect of the reaction is one that
makes photodynamic therapy so efficient. The treatment
can be continued for an extended period of time without
the need for reinjection of the photodynamic drug and wait
time for circulation.
THE SCIENCE BEHIND
PHOTODYNAMIC THERAPY
The technology of photodynamic therapy uses
chemical and biological processes to carry out its functions
and also uses engineering skills to heighten the efficiency
of the system. PDT uses a single drug and light; the
combination of the two destroys the affected area. This
drug is called a photosensitizer. There are different
sensitizers that can be used and each one has different
effects, which will be discussed later in this section. The
photosensitizer harnesses the energy from the source of
light directly. This energy is transferred to molecular
oxygen which in turn forms singlet oxygen, which is an
activated form of oxygen. and it is then ready to travel to
the affected area [7]. These drugs are able to move directly
to the tumor with minimal damage to healthy cells. Like
photosensitizers, there are many different drugs used that
have different effects. This singlet oxygen is a pure
cytotoxic free radical that attacks cellular components.
Regeneration of the photosensitizer is important because it
allows it to act as a catalyst. Singlet oxygen occurs rapidly
for each sensitizer molecule [7].
Photosensitizing Agents
Photosensitization is a process in a molecule absorbs
light and undergoes a reaction that produces energy or a
product. These molecules or photosensitizing agents can be
living cells, or certain chemical compounds, like
chlorophyll in plants. Photosensitizing agents or
photosensitizers are what drive photodynamic therapy,
they are essentially the active ingredient in the
photodynamic drug [7]. In oncological photodynamic
therapy, there are two different reactions that are used to
eradicate the cancer cells. Each involve the activation of a
photosensitizer with electromagnetic radiation to release
high energy form of oxygen that destroys the cancer cells.
Both reactions occur in the same manner but produce
The Chemistry Behind Photodynamic Therapy
As discussed previously, there are two different
reactions that can occur in photodynamic therapy. In a
Type I photosensitization reaction, a photosensitizer is
excited when exposed to electromagnetic radiation because
it absorbs a photon from the light. When the
photosensitizer is excited it undergoes an internal reaction
that leads to chemical changes to the molecule. The
2
Austin Blair
Gabrielle Robinson
addition of the photon causes a “one-electron transfer
reaction” where a radical ion is produced in both the
sensitizer and substrate, or carrier molecule. Usually an
electron is transferred from the substrate to the
photosensitizer to produce substrate radical cation and a
photosensitizer radical anion. These free radicals further
react with the oxygen in the blood to produce a superoxide
radical anion which is used in cancer cell treatment. Type
II reactions follow the same steps as a Type I reaction. A
photosensitizer is excited when exposed to electromagnetic
radiation however, there is no electron transfer between a
substrate
and
the
photosensitizer.
Once
the
photosensitizing agent is excited it transfers an electron to
a ground state oxygen molecule, which turns into an
excited singlet oxygen [9]. These singlet oxygens are used
to kill cancer cells as well.
take place again [9]. This aspect of the reaction shown in
Figure 1 is one that makes photodynamic therapy so
efficient. The treatment can be continued for an extended
period of time without the need for reinjection of the
photodynamic drug and wait time for circulation.
Singlet oxygens are the molecules that travel to the
tumor. A singlet oxygen is defined as the lowest state of
the dioxygen molecule. This is considered the cytotoxic
free radical which is a very reactive form of oxygen.
During its state of decay, the singlet oxygen molecule emits
infrared radiation [10]. The emission of infrared radiation
is what makes singlet oxygen so dangerous to the cells,
causing the deaths of malignant cells. These molecules
specialize in targeting the mitochondria, DNA, and lipid
membranes of the cells. As the cells endure the attack, they
eventually break down and die due to the free radical
attacking the microstructures. This chemical process of a
dioxygen molecule transitioning to its excited state and
becoming very reactive is what causes necrosis and
apoptosis to occur.
Superoxide is an oxygen molecule with an extra
electron, giving it its high excess of energy. Superoxide is
very harmful to human cells because it causes mutations in
DNA as well as attacks the enzymes that make other
essential molecules [11]. The ability for superoxide to
destroy cells is harnessed and focused only on the tumor
cells in photodynamic therapy. Superoxide is only
produced in the contained area of the tumor that is exposed
to light. It breaches the melanoma cells and causes
mutations in their DNA which leads to the death of the cell,
effectively destroying the tumor without harming healthy
cells.
FIGURE 1 [9]
Type I vs. Type II reactions, displaying the different
products.
The Biology Behind Photodynamic Therapy
Once a photosensitizing drug is injected into the
bloodstream, the molecules circulate through the body for
up to 72 hours. During this period the drug is able to
infiltrate the tumor and get into the cancer cells [4]. Many
photosensitizers on their own could not break through the
cell membranes due to the chemical nature of the
molecules. This is where the carrier molecule comes into
play. Certain molecules are taken up by the cells much
easier than others and they are designed to carry
photosensitizers, making the drug more efficient. The
cancer cells uptake the photosensitizing drug through the
cell membrane and once activated, the photosensitizer will
destroy the cell from the inside. Some photosensitizers can
even cause direct damage to the DNA by attaching itself
between the DNA strands in the double helix [12]. Other
techniques, like the one shown in Figure 3 below, involve
attaching the photosensitizer to the outside of a cell and
destroying it that way.
FIGURE 2 [10]
Further explanation of photodynamic reactions.
In both reactions, the photosensitizing agent is
reproduced as a final product which allows the reaction to
3
Austin Blair
Gabrielle Robinson
FIGURE 4 [13]
Process of cell death by apoptosis.
FIGURE 3 [11]
Superoxide (red) attacking an enzyme and causing a
reaction that will destroy it, similarly to how it
destroys a cancer cell.
Figure 4 shows the step by step process of Apoptosis.
Apoptosis is essentially something that happens in the
human body naturally. For example, in the womb, every
fetus has webbing that connects the digits of the hands and
feet. Apoptosis causes this webbing to disappear [14]. This
shows that apoptosis is more natural than necrosis and that
is why it is used more often. These certain biological
processes cause the cells of the tumor to die off and
terminate the cancer.
As previously mentioned, the two ways that the free
radicals attack the tumor are necrosis and apoptosis.
Necrosis is considered an unprogrammed cell death while
apoptosis is programmed. Necrosis is when blood cannot
flow to the cell and it is starved of oxygen and cannot
survive. This process often has repercussions. These cells
that die from starvation can release harmful chemicals that
harm healthy cells. It is also difficult for phagocytes to
“clean up” the immune system after the death because it
does not send cell signals to make sure the phagocytes
destroy the dead cell [13]. Apoptosis, however, has a
cleaner technique, and is more commonly used. It is often
referred to as a cell “committing suicide [14].” Proteins
called caspases break down components that the cell needs
to survive. Next, the production of enzymes called DNases
increases and destroys the DNA of the cell, killing it
completely.
Light Advancements
Light delivery systems play an extremely
important role in photodynamic therapy. The lasers must
be safe for the patient as well as having the ability to
effectively excite and activate the photosensitizing agent.
For this reason, advancements in light delivery systems
have been huge proponents in the improvement of
photodynamic therapy. Plenty of light advancements have
been made in order to improve the efficacy of PDT. An
adequate dose of light is often always available to be
delivered to a tumor which makes PDT rarely rejected due
to an insufficient supply of light. The new availability of
diode lasers has increased the efficiency because these
lights are portable, small, reliable, and fairly inexpensive,
totaling around $20,000 or less [8]. This is a better price
compared to previous PDT lasers. They are also favored
because they do not require much technical skill to
understand how to handle them. The one limitation of these
diode lasers is that they only emit a certain wavelength and
therefore can only be used for a certain photosensitizer.
This makes them somewhat less useful for skin cancer PDT
4
Austin Blair
Gabrielle Robinson
research because many different photosensitizers are being
assessed. Many non-laser sources have also been
developed that include different filtered lamps and in
recent years, light-emitting diodes [8].
The electromagnetic radiation sources are usually
lasers or LEDs and can deliver the light to the tumor with
pinpoint accuracy. Recent breakthroughs in light delivery
include the development of fiber optic lasers that may help
reduce the cost of photodynamic therapy. Metal vapor
lasers are portable lasers that do not require a specialized
electrical supply of water cooling which adds to the ease of
use. Diode lasers are also portable and have built in air
cooling systems, they also only need a 120-volt power
sources which is what a standard wall outlet supplies.
Perhaps the biggest advantages of new and improved light
delivery systems is the computer programming of the lasers
to accurately administer the light where needed and reduce
human error in use of the laser [15].
the drug only infiltrates the tumor cells, reducing the
number of healthy cells that are damaged in the area where
the light is shone [7]. This improves not only the efficiency
of PTD but the efficacy as well. Nonporphyrin
photosensitizing agents have not been heavily researched
until the past 8 years or so and are in the early stages of
development. They are structured and work differently
than normal porphyrin based photosensitizers, as displayed
in Figure 4 below, but have the potential to be very helpful
in the future of photodynamic therapy.
Photosensitizing Advancements
The biggest advancements made in photodynamic
therapy are those made in the photosensitizing aspect.
Making the photosensitizing agents more efficient, being
able to create more energy and destroy cancer cells more
effectively, as well as being able to navigate the blood
streams with greater ease have major impacts on the
treatment of skin cancer with photodynamic therapy.
Traditional photodynamic therapy uses porphyrin
photosensitizers. In recent years, the first and second
generation photosensitizers have been falling behind and
have required new innovations to be made. Recently
preclinical and clinical advancements have been made in
newer generation porphyrin photosensitizers, as well as,
nonporphyrin photosensitizers [7].
Porphyrin bases photodynamic agents belong to a class
of molecules called tetrapyrroles. Tetrapyyroles are a
major component in the hemoglobin and myoglobin, the
oxygen binding proteins in blood. Porphyrins possess a
highly conjugated, heterocyclic macrocycle that is bonded
to a central metallic atom like iron or magnesium. The
reason that porphyrins are good photosensitizers is because
the molecules hold a large number of pi bonds which
allows them to absorb long wavelength light more
efficiently than other types of molecules [7]. Having
similar structure and properties to hemoglobin also allows
them to attach to the red blood cells and move throughout
the body with greater ease. Many of the advancements
made in the third-generation porphyrin photosensitizers
has been made by conjugating or packaging the secondgeneration photosensitizers into more effective carrier
molecules that deliver the drug to the specific tumor area.
This is possible because tumor cells have surface antigens
that are far different than those of normal cells. Certain
monoclonal antibodies, liposomes, and polymers can
selectively bind to the abnormal surface antigens, meaning
FIGURE 4 [7]
Examples of first, second, and third generation
photosensitizers and their chemical structures.
Recently boron dipyrromethene based photosensitizers
have shown promise as a newly developed photosensitizer
that will further the efficiency of oncological treatment
with photodynamic therapy. These compounds are very
large molecules that consist of six-membered ring of
dipyrrole and methine units, a central boron atom, and two
five-membered rings on the outside. The boron
dipyrromethene has very ideal photodynamic and
fluorescent properties. It produces very intense
fluorescence quantum yields, has a very sharp excitation
and emission spectrum, as well as, a highly stable photo
and chemical nature [16]. The intense fluoresce of boron
dipyrromethene means it gives off very high energy singlet
oxygens, making a more powerful drug, and as discussed
5
Austin Blair
Gabrielle Robinson
before an ideal photosensitizer is an extremely stable
compound under normal conditions. These properties
make boron dipyrromethene an exciting new breakthrough
in the research of new photosensitizing agents.
Research
of
aza-boron
dipyrromethene
photosensitizers has proven even more successful than the
normal boron dipyrromethene photosensitizers. The azaboron version exhibits a very high generation of singlet
oxygen, a “relatively good” emission spectra, and a very
large molar extinction coefficient, higher than that of the
regular boron dipyrromethene. The molar extinction
coefficient is the number of cells that are destroyed with
one mole of the photosensitizer per centimeter. The molar
extinction of aza-boron dipyrromethene is 75,000 M-1cm-1
which is an exceptional molar extinction value. Another
exciting discovery about aza-boron dipyrromethene is that
it exhibits these characteristics with an activation
wavelength that is much lower than that of normal
photosensitizers. The aza-boron photosensitizer is
activated by light in the far-red region of the
electromagnetic spectrum, from 650 nanometers to 680
nanometers [16]. Although it is somewhat smaller than the
ideal wavelength, the wavelength is not too much smaller
that it will cause harm to the healthy cells. The ability for
this compound to produce such great results at a lower
wavelength makes it a much more efficient photosensitizer.
effectiveness. Another treatment of skin cancer is
chemotherapy. This is a type of radiation therapy that gets
rid of a tumor and usually prevents it from reoccurring. The
problem with chemo is that there are many harmful side
effects including extreme fatigue, discomfort, loss of
senses, and hair loss. This is mainly the reasons why
chemotherapy is not the most common treatment for
melanoma skin cancer since PDT has become available. It
may relieve some symptoms but does not perform as
effectively on melanoma skin cancer compared to other
cancers. Cancer treatments can also be very pricey, but
PDT costs between $2,000 and $3,500 which is much less
than other cancer treatments like chemotherapy for
example, which can cost up to $30,000 [17] [18].
Dual Selectivity
One of the biggest advantages of photodynamic therapy
over tradition treatments is its lack of major side effects.
The main reason for this is dual selectivity. Traditional
cancer treatments are not selective at all, attacking healthy
cells as well as the cancer cells. This causes effects such as
loss of hair, and fatigue [15]. Photodynamic therapy is a
highly selective therapy on two levels, hence it being
dually selective. The photodynamic drugs are only
activated when exposed to light and the only region that is
effected is the targeted area. The second level of selectivity
is now the ability to make photosensitizers that only attach
to and infiltrate cancer cells like many of the thirdgeneration porphyrin photosensitizing agents. These
different levels of treatment selectivity place
photodynamic therapy ahead of all other treatments in
terms of reducing side effects which has major implication
in choosing between treatment options.
ADVANTAGES AND DISADVANTAGES
OF PHOTODYNAMIC THERAPY
Comparison to Traditional Treatments
Although PDT seems like a very viable option for
treating skin cancer, there are many other options for
certain situations. This means that PDT is not necessarily
in competition with other treatments, but may be a better
fit at times. Laser therapy is a classic attempt at getting rid
of a tumor. A study was conducted to determine the
successes of laser therapy (LD), laser photo destruction
(LPD), and PDT [6]. There were 1535 patients. Of that
number, 112 patients used LD. This treatment was used on
patients with very small tumors with a 1-1.5 cm diameter.
The closing of the laser wound was covered by the
transported skin flap. Out of all the patients, three tumors
reappeared. The LPD group contained 1341 patients. It was
performed on patients with the same tumors as the LD
patients and on patients with superficial tumors of body
and extremities that had a diameter up to 5 cm. Within 2.58 months, tumor reoccurrence was found in 22 patients.
PDT was performed on 82 patients with plenty of larger
tumors that kept reoccurring and tumors in inconvenient
locations on the face. There was no tumor reappearance on
any of these patients. Although the other laser treatments
did have very successful rates of tumor elimination, this
shows that the tumors with high rates of reoccurrence were
completely rid by PDT, and therefore demonstrates the
Limitations of PDT
One of the limitations of PDT is that the light used
cannot pass through more than one centimeter of skin.
Therefore, the therapy can only be used on tumors on the
walls or cavities of internal organs, on the skin, or just
under the skin. It also cannot be used on cancer that has
metastasized, or spread [4]. After the drug is injected into
the patient’s body, it leaves their skin and eyes very
sensitive to light for up to six weeks after the treatment.
This calls for special precautions that need to be taken after
the drug has entered, like avoiding bright outdoor sunlight
for the six weeks of sensitivity [4]. Although the
photosensitizing drug travels to the tumor and the
electromagnetic radiation is localized in just that area, there
still may be some damage that can occur in the surrounding
area. There may be scarring of the tissue around the tumor,
burns, swelling, and pain. Some other side effects may
include coughing, trouble swallowing and breathing, and
stomach pain [4]. These side effects, however, are usually
temporary.
6
Austin Blair
Gabrielle Robinson
face and to determine the probability of patients to prefer
surgery or PDT for skin cancer removal. After the PDT
treatment, patients were told to stay in a darker room for at
least 48 hours, and use sunscreen before they went outside.
Thirty-four patients were tested. These patients had
previously had the skin surgery and decided to try PDT.
About 17 patients said they would prefer surgery over
PDT, and six patients preferred PDT. Five patients
believed they had the same results, five were bot
contactable, and one person declined to answer [20].
WHERE IS PHOTODYNAMIC THERAPY
HEADED?
Future of Photodynamic Therapy
Over the past decade, thousands of patients have been
treated by PDT, and have had plenty of success, as
previously mentioned. PDT is used widely in
dermatological oncology, but less in other situations [6].
Will PDT become more popular and more mainstream in
the future? Most people have never heard of this treatment.
Will this change, and could it soon be the most popular
treatment for skin cancer? Ethical dilemmas always rise
with new innovations. Many hospitals resist this new
treatment because they prefer the more traditional
treatments. It was also very difficult to get inexpensive and
convenient light sources. Now that this is not much of a
problem anymore, this allows PDT to expand as a more
routine treatment. One problem that still exists is the fact
that we need improved, more selective drugs to sustain skin
photosensitivity. This will surely increase the advantages
of PDT by making this minimally invasive, and making in
more convenient on the patient and practitioner [6]. A new
photosensitizing drug, called Photoclor(PHHP), is being
tested to improve the process of PDT. It may be able to
treat tumors that are located very deep in the skin and
become even more localized for treating cancer cells only.
Studies show that this drug decreases the amount of time a
patient is sensitive to light after therapy. This drug can also
be removed from the body faster than other
photosensitizing drugs. There are also studies being
conducted to try and reduce the side effects of PDT by
using different ointments on the affected area. These
ointments contain cobalt ions and ferrous. Scientists are
trying to also use hydrogen peroxide to improve the results
of PDT. Other light sources that are being developed that
may be able to activate the drugs with a fewer dose, which
will in turn reduce the side effects. These new
advancements will allow PDT to reach its fullest potential
in the future [19].
QUALITY OF LIFE IS MAINTAINED
WITH PHOTODYNAMIC THERAPY
In the most general of terms, sustainability is the ability
to maintain the current state at a certain rate or level.
Sustainability is mostly thought and talked of in terms of
ecology and the environment, stating that sustainability is
the ability to preserve the current state of the earth for
future generations by using renewable resources or finding
more environmentally friendly methods of production.
Photodynamic therapy may not contribute to the
sustainability of planet earth but is a sustainable process in
different respects. Sustainability in terms of bioengineering
and medicine means the ability to maintain an individual’s
quality of life and or health. Photodynamic therapy has the
ability to maintain and even improve a skin cancer patient’s
quality of life, as well as restoring cancer patients to their
prior state of health.
There are numerous ways in which photodynamic
therapy helps patients maintain their current quality of life,
which are all reasons why photodynamic therapy is a
sustainable innovation. Photodynamic therapy has no longterm side effects, compared to other treatments that may
have a huge effect on a patient’s everyday life. Traditional
chemotherapy drugs can cause major fatigue which
weakens a patient’s ability to do everyday tasks. As stated
before, photodynamic drugs are only active in the site of
the tumor, which eliminates the side effects elsewhere in
the body. The lack of side effects and fatigue from
photodynamic therapy allows patients to continue their
everyday lives without issue. One major example of this is
the fact that chemotherapy can also lead to hair loss, while
photodynamic therapy does not. Losing one’s hair may
take a large emotional toll on the individual, reducing their
quality of life; with photodynamic therapy their quality of
life is preserved. Photodynamic therapy is a minimally
invasive treatment which leaves little to no scarring unlike
most traditional surgeries for skin cancer. Scarring could
have a similar effect as hair loss on the patient, leading to
emotional stress, but this possibility is eliminated in
photodynamic therapy. Perhaps the biggest way
photodynamic therapy preserves a patient’s quality of life
is the fact that in most cases it is an outpatient treatment
and it is very quick. This means that the patient is able to
Choosing Otherwise
Topical treatments like PDT do have side effects like
persistent pain on the affected area for some time. This may
be why patients in a study stated that they would prefer
surgery over PDT [16]. Patients should understand this
before they agree to this treatment to determine if surgery
or PDT is the correct choice. Many people just prefer
traditions over change. This is similar with the hospitals. A
study was conducted at Australian College of Cutaneous
Oncology to show the different results between surgery and
PDT. The purpose of this study was to take patients who
have undergone surgery and PDT for skin cancer of the
7
Austin Blair
Gabrielle Robinson
remain at home during the treatment process and spend
minimal time at the hospital or treatment facility, as
opposed to other treatments which may be lengthy and
require the patient to spend extended periods of time at the
hospital. Photodynamic therapy is also very efficient form
of treatment. Many new photodynamic agents are
regenerative and reproduce during the reaction, allowing a
single treatment to last a longer period of time, reducing
the frequency of treatments. Radiation therapy can only be
sustained in a single area for a very short period of time
because of the risks of further gene mutation. Due to this
fact, a person being treated with photodynamic therapy
have far fewer treatments than an individual undergoing
radiation therapy. Each of these advantages over traditional
treatments is a significant step towards preserving a skin
cancer patient’s quality of life, possibly making it the most
sustainable treatment option offered.
As well as being humanely sustainable, photodynamic
therapy is economically sustainable, meaning that it’s able
to be supported, fiscally, in the long run Photodynamic
therapy is also sustainable for both parties, the patient and
the treatment centers. In respect to the patient,
photodynamic therapy is much cheaper than some other
treatments, costing as little as $2,000. The low cost allows
many people the ability to pay for it without worry of it
taking an economic toll on them. The regenerative aspect
of photodynamic drugs is also a reason why photodynamic
therapy is an economically sustainable treatment,
especially for the treatment center. Since the drug
regenerates itself the treatment center needs less of the
drug, so they are spending less money and less resources
are being used to produce the drugs because the amount
needed is a fraction of what it would be if the drugs didn’t
regenerate.
a perfect example of why PDT is more efficient than other
treatments because they can attack other cells that are
healthy. PDT is not detrimental to the body in that way
which makes it more appealing than chemotherapy and
laser therapy. Photodynamic therapy is a breakthrough
innovation that will most likely have a bright future in the
medical field for skin cancers as well as other cancers.
SOURCES
[1] D. Dolmans, D. Fukumara, R. Jain. “Photodynamic
Therapy for Cancer.” Nature Reviews. 03.2003. Accessed.
02.17.2017.
http://www.nature.com/nrc/journal/v3/n5/full/nrc1071.ht
ml
[2] “Skin Cancer Facts and Statistics.” Skin Cancer
Foundation.
02.02.2017.
Accessed.
02.15.2017.
http://www.skincancer.org/skin-cancer-information/skincancer-facts
[3] “Melanoma Statistics.” Cancer.Net. 07.2016.
Accessed. 02.15.2017. http://www.cancer.net/cancertypes/melanoma/statistics
[4] “Photodynamic Therapy for Cancer.” National Cancer
Institute.
09.06.2011.
Accessed.
01.10.2017
https://www.cancer.gov/aboutcancer/treatment/types/surgery/photodynamic-fact-sheet
[5] E. Stranadko M.D, O. Skobelkin, Y. Makeev, N.
Markichev, M. Riabov, A. Armtchev, M. Muraviov. “Laser
Treatment of Skin Cancer: Dissection, Photodestruction
and Photodynamic Therapy.” 11.04.1996. Accessed.
01.25.2017
https://www.engineeringvillage.com/search/doc/abstract.u
rl?pageType=quickSearch&usageOrigin=searchresults&u
sageZone=resultslist&searchtype=Quick&SEARCHID=f
ca3106eM05b2M4946M9972Mce7d6ac68735&DOCIND
EX=2&database=1&format=quickSearchAbstractFormat
&dedupResultCount=&SEARCHID=fca3106eM05b2M4
946M9972Mce7d6ac68735&referer=%2Fsearch%2Fresul
ts%2Fquick.url
[6] University of North Carolina at Chapel Hill.
“Researchers Use Light to Launch Drugs from Red Blood
Cells.” Science Daly. 01.04.2017. Accessed. 01.10.2017.
https://www.sciencedaily.com/releases/2017/01/17010414
3603.htm
[7] A. O’Connor, W. Gallagher, A. Byrne. “Porphyrin and
Nonporphyrin Photosensitizers in Oncology: Preclinical
and Clinical Advances in Photodynamic Therapy.”
Photochemistry and Photobiology. 03.08.2009. Accessed.
03.01.2017.
http://onlinelibrary.wiley.com/doi/10.1111/j.17511097.2009.00585.x/full
[8] S. Brown. “The Present and Future Role of
Photodynamic Therapy in Cancer Treatment.”
ScienceDirect. 08.2004. Accessed. 01.10.2017.
http://www.sciencedirect.com/science/article/pii/S147020
4504015293
PHOTODYNAMIC THERAPY: SOON TO
BE THE FIRST CHOICE IN SKIN
CANCER TREATMENT
After analyzing the process of photodynamic therapy,
and considering the side effects of the new technology, it
is clear to see that PDT definitely has its advantages over
traditional skin cancer treatments. As PDT becomes more
common in the hospital workplace, more patients will
begin to see its benefits and be able to compare it to the
other treatments to see if it is the right fit for them. This
will most likely increase the percentage of people that
choose PDT. While engineering innovations continue to
evolve, photodynamic therapy has plenty of opportunity to
make huge advancements within the coming decades.
Engineers work to improve the efficiency of technologies.
In the coming decades, engineers may be able to speed up
the delivery process or even try to fix the problem with the
sensitivity to light post-therapy. As we can see, the drug is
only activated specifically at the site of the tumor. This is
8
Austin Blair
Gabrielle Robinson
[9] N. Oleinck. “Basic Photosensitization.” Department of
Radiation Oncology Case Western Reserve University
School of Medicine. 09.09.2011. Accessed. 02.24.2017
http://photobiology.info/Oleinick.html
[10] “What is Singlet Oxygen.” California State University
Los Angeles Department of Chemistry and Biochemistry.
2016.
Accessed.
02.22.2017.
http://www.calstatela.edu/dept/chem/selke/r-1.htm
[11] “Superoxide Dismutase (SOD) - The Good –
Superoxide – The Bad – Disease – The Ugly.” Cancer Cell
Treatment.
03.26.2016.
Accessed.
02.22.2017.
http://cancercelltreatment.com/2016/03/26/superoxidedismutase-sod-the-good-superoxide-the-bad-disease-theugly/
[12] T. Christensen. “Photosensitization of Subcellular
Structures.” Norwegian Radiation Protection Authority.
06.04.2009.
Accessed.
02.07.2017.
http://photobiology.info/Christensen.html
[13] M. Edmonds. “What is Apoptosis.” How Stuff Works.
03.31.2010.
Accessed.
02.07.2017.
http://science.howstuffworks.com/life/cellularmicroscopic/apoptosis.htm
[14] B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts,
P. Walter. “Programmed Cell Death (Apoptosis).” 2002.
Accessed.
02.27.2017.
https://www.ncbi.nlm.nih.gov/books/NBK26873/
[15] I. Yoon, J. Li, Y. Shim. “Advance in Photosensitizers
and Light Delivery for Photodynamic Therapy.”
01.31.2013.
Accessed.
03.01.2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572355/
[16] S. Awuah, Y. You, “Boron Dipyrromethen
(BODIPY)-Based Photosensitizers for Photodynamic
Threapy.”
07.09.2012.
Accessed.
03.02.2017.http://pubs.rsc.org/en/content/articlepdf/2012/
ra/c2ra21404k
[17] “Photodynamic Therapy PTD.” DocShop.
07.03.2015.
Accessed.
03.26.2016.
http://www.docshop.com/education/dermatology/facial/ph
otodynamic-therapy
[18] “Cost of Mesothelioma Treatment.” Asbestos.com.
01.12.2017.
Accessed.
03.26.2017.
https://www.asbestos.com/treatment/expenses/
[19] “Chemotherapy for Melanoma Skin Cancer.”
American Cancer Society. 05.20.2016. Accessed.
02.06.2017.
https://www.cancer.org/cancer/melanomaskin-cancer/treating/chemotherapy.html
[20] A. J. Dixon. “Patients More Likely to Prefer Surgery
to Novel Photodynamic Therapy.” Journal of Clinical &
Experimental Dermatology Research. 06.05.2016.
Accessed 01.10.2017. https://www.omicsonline.org/openaccess/patients-more-likely-to-prefer-surgery-to-novelphotodynamic-therapy-2155-95541000358.php?aid=74435
We would like to recognize Daniel Budny for always
giving us a good laugh, encouraging us to excel in this
paper. We would also like to recognize Julia Hartz, our cochair, for helping us to improve our focus in the paper in
order to improve the paper as a whole.
ACKNOWLEDGEMENTS
9