Photodynamic Therapy For Lung Cancer

  • Alina TariqMaster's degree, Biotechnology and Bioengineering, University of Ken
  • Aisha Din BSc (Hons) Biomedical Science at De Montfort University

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Using ‘light’ for the treatment of cancer: Science fiction or actual science? Photodynamic therapy utilises light-sensitive drugs, that when activated (via a specific light source), allow the drugs to kill cancer cells. 

Definition of photodynamic therapy (PDT)

Photodynamic therapy (PDT) kills small abnormal areas of tissue without the invasiveness of surgery. PDT involves light-sensitive drug(s) and a light source; the drug and the light source are harmless on their own. However, for the drug to exert its therapeutic efficacy (i.e., kill abnormal cells), the light activates the drug, allowing the nearby cells to damage and die.1

Overview of lung cancer

Lung cancer is one of the most commonly diagnosed cancers in the UK with an incidence of 43,000 each year. Lung cancers mainly affect older people (more than four out of 10 people are aged 75 and older), and while individuals who don’t smoke can also develop lung cancer, around 70% of those diagnosed with lung cancers are smokers.2

Unfortunately, there are no signs or symptoms of early-stage lung cancers, but many individuals who are diagnosed with lung cancers develop symptoms such as persistent cough, coughing of blood, persistent breathlessness, unexplained tiredness, weight loss, and/or an ache or pain when breathing or coughing. The lack of noticeable symptoms of lung cancer (before it has spread throughout the lungs) means that the outlook for the condition is not good. About two in five people diagnosed with lung cancer live for at least one year after diagnosis. Despite this, common treatment options such as surgery, radiotherapy, chemotherapy and immunotherapy can be used to treat lung cancer.2 

Purpose of photodynamic therapy for lung cancer

Photodynamic Therapy for lung cancer may be used to treat early-stage lung cancer or for those who are unable or unwilling to have surgery. PDT can also be used if the tumour is blocking the airways.2 However, like all cancer therapies, PDT has its advantages and disadvantages. This paper will discuss the basic principles of PDT, its advantages, and its limitations. 

Understanding photodynamic therapy

Photodynamic therapy is a form of radiation therapy, it works by either applying the light-sensitive drug (photosensitisers) directly to the location of the tumour (local) or by systemic application (a treatment where the drug affects the body as a whole- i.e., via the bloodstream). The photosensitisers accumulate in the abnormal cells/tissues (i.e., the cancerous cells), and become more sensitive to the light.2,3 The induction of a light source (at a specific wavelength), initiates an activation process called reactive oxygen species (ROS), resulting in the selective destruction of cancer cells.4 

Basic principles of PDT

Photosensitisers

Photosensitisers are a vital mechanism of PDT. For lung cancers, a drug called Photofrin is usually administered via an injection.2,4 Once injected into the bloodstream, it takes the drug 6-48 hours to accumulate in the cancerous cells.4 Following the drug administration, light activation takes place .2

Light activation

Upon the introduction of the photosensitisers, a follow-up appointment may be made for the light therapy to activate the drug for it to kill cancerous cells.1 The follow-up appointment may be 24-72 hours after the injection of the photosensitiser. As the photosensitiser makes cancer cells more sensitive to the light, a thin flexible tube with a light at the end (also known as an endoscope) is guided to the site of the tumour.1 This tube with the light source allows the light to destroy photosensitiser-rich cancer cells.2 While the drug itself does not cause pain,3 sometimes a local anaesthetic (numbing of an area) or medication to help the patient relax may be used. Alternatively, general anaesthetic (putting the patient to sleep) may be used while you have the procedure.1 Local and general anaesthetic is usually used to help the patient relax to allow this minimally invasive procedure to take place. 

Reactive oxygen species (ROS) generation

Once photosensitisers are activated upon the introduction of a light of a specific wavelength, they initiate a process called reactive oxygen species (ROS).3,4 ROS are a type of unstable oxygen molecule which can easily react with other molecules in the cell. A build-up of these ROS molecules may lead to the damage of DNA, RNA, and proteins within the cell, thereby causing cell death.5  

While the photosensitisers are administered via an injection, the drug accumulates in the cancerous cells and is only activated when the tumour is targeted by a light of a specific wavelength. The specificity of the photosensitisers only accumulating in the tumour cells and the targeted activation via the endoscope, allows the ROS to generate in the specific treatment area. The specific localisation of the ROS, therefore, kills tumorous cells.

Mechanism of action in cancer cells

Cells have DNA, which is essentially instructions required for the cells to develop, survive and reproduce.6 Therefore, the integrity of the DNA must be maintained for the organism to survive. However, the DNA may become damaged due to smoking or random chance, resulting in mutations and leading to cancer. To protect the organism, an important biological strategy is in play to maintain the vital instructions for survival - the activation of programmed cell death. This allows the cell to die, preventing further harm to the cell and the organism.7 

The mainstay for cancer treatments is to utilise programmed cell death to induce DNA, RNA, and protein damage, triggering innate programmed cell death (apoptosis).7 Similarly, PTD activates apoptosis where the accumulation of ROS, may lead to the damage of the DNA, RNA, and proteins within the cell, thereby causing cell death.5 

Advantages of photodynamic therapy

To treat lung cancers, surgery, radiotherapy and chemotherapy are usually used.2 However, these therapies are invasive and have numerous complications. For example, the ‘gold standard’ care for individuals with early-stage lung cancer is a surgical procedure called a lobectomy (removal of a section of the lung).4 A lobectomy is highly invasive and patients can have a risk of infection.2 Chemotherapy also comes with its complications as cancers can become resistant to chemotherapy drugs, the high toxicity that comes with the therapy results in a weakened immune system (making the patient more susceptible to infections), and it can lead to being and feeling sick, hair loss, tiredness, etc.2,4

PDT is an underutilised form of treatment against lung cancers. PDT has reduced chances of drug resistance and reduced toxicity.4 PDT is also less invasive compared to surgery (leaves no scars), more targeted to the tumour, and has minimum systemic side effects. Furthermore, PDT can be used in combination with other cancer therapies, such as surgery and chemotherapy.8 

Challenges and limitations

Like all therapies, PDT can present with its challenges and limitations. In dense/ large tumours, it could be possible that the drug is unable to penetrate through to the whole tumour. Due to how compact the tumour becomes, the distribution of the photosensitiser is impaired, resulting in the treatment having reduced effectiveness in eliminating all cancerous cells.8 Another limitation of PDT is that it is mainly used for localised tumours, it cannot be used for cancers that have spread (metastasised). Additionally, as mentioned above, there are no signs or symptoms of early-stage lung cancer, meaning that by the time the lung cancer is detected and diagnosed, PDT therapy is unsuitable as the tumour is either too dense or the cancer has metastasised.2 

Future directions and research

To address the constraint of limited drug penetration in tumorous cells, research is being conducted in nanoparticles. Nanoparticles combine chemistry, biology, applied physics, and materials sciences to design structures which allow for drug delivery while circumventing biological barriers (i.e., the inability for drugs to penetrate through to the tumour, due to the denseness of cells).4 In fact, a study has shown that when lung cancer cells were grown to 21mm3 in mice using nanoparticles along with a photosensitiser drug, it helped not only visualise the tumours but effectively slowed their growth.9 While the use of nanoparticles greatly enhances drug delivery to the tumour site, the research is still in its infancy as human trials are essential to validate the safety and efficacy of this approach. So, despite the promising results in preclinical studies, translating nanoparticle-based PDT into clinical applications requires rigorous testing to ensure its feasibility and minimise potential side effects.

Summary

Lung cancer is one of the most commonly diagnosed cancers in the UK, and while surgery and chemotherapy are the main treatments for lung cancer, these therapies are invasive, toxic, and can present numerous health complications. Photodynamic therapy is systematically administered via the blood, where the photosensitiser drug accumulates in the cancerous cells. The photosensitiser drug is then activated using a specific wavelength of light for the drug to initiate the induction of ROS. The build-up of ROS results in damage to the DNA, which in turn triggers the cells’ innate apoptotic mechanism, killing the cancerous cells. While the side effects of PDT are negligible compared to the side effects of chemotherapy and surgery, a limitation of using PTD is the inability of the photosensitiser drug to penetrate the whole tumour. To overcome the limitation of drug penetration, scientists are using nanoparticles for the efficient delivery of photosensitiser drugs to the tumour. In mouse models, the nanoparticle-based PDT has shown promising results, however, more research needs to be completed to ensure the feasibility of the nanoparticle-based PDT and to mitigate any potential risks that may arise. 

References

  1. nhs.uk [Internet]. 2017 [cited 2024 Feb 6]. Photodynamic therapy (Pdt). Available from: https://www.nhs.uk/conditions/photodynamic-therapy/ 
  2. nhs.uk [Internet]. 2017 [cited 2024 Feb 6]. Lung cancer. Available from: https://www.nhs.uk/conditions/lung-cancer/
  3. Castano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy: part one—-photosensitizers, photochemistry and cellular localization. Photodiagnosis Photodyn Ther [Internet]. 2004 Dec [cited 2024 Feb 6];1(4):279–93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108220/
  4. Crous A, Abrahamse H. Photodynamic therapy of lung cancer, where are we? Frontiers in Pharmacology [Internet]. 2022 [cited 2024 Feb 6];13. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.932098
  5. Https://www. Cancer. Gov/publications/dictionaries/cancer-terms/def/reactive-oxygen-species [Internet]. 2011 [cited 2024 Feb 7]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/reactive-oxygen-species
  6. Deoxyribonucleic acid (Dna) fact sheet [Internet]. [cited 2024 Feb 7]. Available from: https://www.genome.gov/about-genomics/fact-sheets/Deoxyribonucleic-Acid-Fact-Sheet
  7. Borges HL, Linden R, Wang JY. DNA damage-induced cell death. Cell Res [Internet]. 2008 Jan [cited 2024 Feb 7];18(1):17–26. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626635/
  8. Wang K, Yu B, Pathak JL. An update in clinical utilization of photodynamic therapy for lung cancer. J Cancer [Internet]. 2021 Jan 1 [cited 2024 Feb 7];12(4):1154–60. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797657/
  9. Huang WT, Chan MH, Chen X, Hsiao M, Liu RS. Theranostic nanobubble encapsulating a plasmon-enhanced upconversion hybrid nanosystem for cancer therapy. Theranostics [Internet]. 2020 Jan 1 [cited 2024 Feb 8];10(2):782–96. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929987/ 

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Alina Tariq

Master's degree, Biotechnology and Bioengineering, University of Kent

Alina is a Master's graduate in Biotechnology and Bioengineering with a background in Medical Biology. Her speciality lies in chemotherapeutic resistance to cancers , igniting her passion for harnessing biotechnology to combat cancer. She is a passionate advocate of Equality, Diversity and Inclusion- especially in healthcare, with a certification in GCP. Alina is confident in her ability to contribute to projects that require scientific expertise and effective communication strategies in order to bring positive changes to the healthcare industry.

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