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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