The therapeutic properties of light have been widely studied for thousands of years but it has been implemented in the clinical platform in the last century. Considering all the challenges and difficulties in the conventional treatment of cancer, new treatment alternatives are highly necessary. Photodynamic therapy (PDT) is a relatively new, minimally invasive therapeutic alternative that efficiently controls the spread of cancer. It is a well-established medical treatment that uses a combination of a light source and a photosensitizer (PS) or photosensitizing agent to destroy cancer cells. The source of the light can be a laser or other source, such as LEDs.

What Is Photodynamic Therapy and How Does It Work?

Photodynamic therapy is a clinically approved, minimally invasive medical procedure that involves the administration of a photosensitizer followed by irradiation at a wavelength that results in a selective cytotoxic activity toward malignant cells. In this therapy, light energy is combined with a drug called photosensitizer. Upon exposure to a high-intensity light, these photosensitizers become toxic. Photosensitizer (PS) molecule, upon being excited by light at a specific wavelength, reacts with oxygen and generates oxygen radicals, singlet oxygen and triplet species in target tissues, leading to cell death. These photosensitizers are used to destroy cancerous and precancerous cells. The photosensitizer remains non-toxic until it is activated by light. PDT may also be called photoradiation therapy, phototherapy, or photochemotherapy. Photodynamic therapy uses 3 components:
i. A photosensitizer
ii. A light source
iii. Oxygen

In case of skin cancer, photosensitizers are topically applied to the skin, which induce certain abnormal cells to produce light-absorbing molecules called porphyrins. The next step is to shine a laser light onto the affected area on the skin to activate the photosensitizer. This light source can be blue, red light, or intense pulsed light (IPL). The treatment can also be possible in natural daylight. Clinicians will decide the best light source for the individual. When the photosensitizers get activated by the light, it reaches the excited singlet state. This singlet state can undergo intersystem crossing to the long-lived triplet state. Photosensitizers in triplet state interact with molecular oxygen and produce reactive oxygen species (ROS) which induces cell death through apoptosis, cellular necrosis or autophagy.

Photodynamic therapy is mainly used as a local treatment. Photosensitizer drugs are currently being used to treat a variety of diseases such as acne, psoriasis and several cancers, such as skin, lung, bladder, pancreas, brain, esophagus, and head and neck. The US Food and Drug Administration (FDA) has approved several photosensitizing agents to treat certain cancers or pre-cancers. The two most widely used photosensitizers are:
i. Porfimer sodium (Photofrin) is used to treat certain kinds of cancers of the esophagus and lung.
ii. Aminolevulinic acid (ALA or Levulan) is used to treat actinic keratosis (AK).
Currently, the FDA has approved photodynamic therapy to treat few diseases such as basal cell skin cancer, esophageal cancer, non-small cell lung cancer, squamous cell skin cancer, actinic keratosis, advanced cutaneous T-cell lymphoma, Barrett’s esophagus.

How Does Photodynamic Therapy Treat Cancer?

The introduction of light into cancer treatment provides a precise tumor localisation of treatment. When cells that have absorbed photosensitizers are exposed to a specific wavelength of light, the photosensitizers produce a form of oxygen, called reactive oxygen species (ROS), that kills them. Antitumor effects of PDT results from three different interrelated mechanisms- direct cytotoxic effects on tumor cells, damage to tumor vasculature and induction of an inflammatory reaction. This may trigger the immune system to attack tumor cells. The time between PS administration and light exposure is called the drug-to-light interval. The effectiveness of this therapy depends upon the type and dose of photosensitizer used, drug-to-light interval, light dose and its fluence rate.

Benefits of Photodynamic Therapy

Findings have demonstrated that PDT is more effective than surgery or radiation therapy in treating certain kinds of cancers and pre-cancers. It has some advantages, such as:
i. Photodynamic therapy does not cause scarring, which makes it a good option for people with skin cancers.
ii. No known long-term side effects have been reported.
iii. It is more often done as an outpatient procedure.
iv. Less invasive and more precise antitumor activity compared to other treatments like surgery.
v. Rapid procedure and it often costs less than other treatments.
vi. The procedure can be repeated, unlike radiation therapy.

Drawbacks of Photodynamic Therapy

i. Sometimes, PDT can harm normal cells in the treatment area and cause side effects.
ii. The light used in photodynamic therapy cannot pass through more than about 1/3-inch of tissue. So, PDT can only be used to treat tumors where light can reach. Therefore, it cannot treat large cancers or cancers that have grown deeply into the skin or other organs.
iii. The photosensitizers used for PDT make people very sensitive to light for as long as 3 months after the procedure. A type of photosensitizer called porfimer sodium makes the skin and eyes sensitive to light for about 6 weeks.
iv. PDT cannot be used to treat certain blood diseases.

Side Effects of Photodynamic Therapy

Like any other medical procedure, PDT carries few risks. Although damage to normal cells is limited, photodynamic therapy can still cause burns, swelling, pain in the treatment area. Other side effects are coughing up blood, difficulty swallowing, breathing problem, skin problems, such as redness, swelling, or itching.

PDT is considered to be a new and promising therapeutic strategy. It has shown its full potential in antitumor activity. Reduced long-term morbidity and the fact that it can be repeated without compromising its efficacy are significant limiting factors for chemotherapy and radiotherapy. However, it can also be combined with other types of treatment, such as surgery and radiation therapy. Future possibilities include other combination treatments with PDT drugs, as well as new PDT drugs that can target tumor cells more precisely and can leave normal cells more quickly and allow the treatment light to penetrate deeper. Finally, it can be stated that in the majority of the critical cases, PDT represents a suitable therapeutic alternative presenting several advantages over the traditional clinical approaches for cancer treatments. Further research is necessary to explore the range of applications of PDT. Scientists believe that a better understanding of this procedure will make more decisive conclusions about PDT’s real potential to become a standard first-line therapy, either alone or in combination with other treatments, for a wide variety of tumors.