Introduction

The definition of a tumour is where an abnormal-sized tissue in the body overgrows, and the cells keep dividing rapidly without dying when they should.  Tumours present in the body may be harmful (malignant) or non-harmful (benign). Benign tumours are able to grow, but they do not spread into nearby tissues and do not infect other parts of the body. However, malignant tumours can invade nearby tissues and spread to the bloodstream and the lymph system.¹ This is a disease known as cancer. 

This article will discuss a special type of treatment named photodynamic therapy (PDT), which targets tumours found in the brain. In general, the PDT offers a targeted and minimally invasive option with promising outcomes.  However, this technique does see some challenges. The limitations and advantages of this technique will be discussed, alongside the future directions to improve this technique. 

How does photodynamic therapy operate? 

Photodynamic therapy is completed via 2 stages and requires the interaction of 3 substrates: oxygen, light, and photosensitizers,⁴ an essential element for successful treatment. 

The photosensitizer can kill cancerous and precancerous cells. Once activated with light, normally with a laser, it becomes toxic towards the targeted area. Afterwards, there is a series of photochemical reactions leading to the generation of reactive oxidative species (ROS). The photosynthesiser reaches an excited state, which contains high energy and is highly unstable. To stabilise itself, it immediately returns to its normal state (also known as the ground state) by releasing excess energy, either as light or heat. The energy release will trigger two main reaction pathways, Type I and Type II, with Type II being the predominant one, as the singlet oxygen it produces serves as the primary cytotoxic agent responsible for the biological damage. Figure 1 shows these molecular mechanisms in detail.

Figure 1. The two main photosensitisation pathways start with a photosensitiser (PS), are depicted in this image. PS achieves an excited triplet state (3 PS ∗) following light absorption. Radicals and ROS are produced in the Type I reaction when an excited PS donates an electron to a biological substrate. The excited PS converts its energy to ground-state oxygen in the Type II reaction, creating extremely poisonous singlet oxygen. In both mechanisms, oxidative damage is caused to the cell, and cellular death is the ultimate result.² 

PDT in the context of brain tumours 

PDT can directly destroy tumour cells by inducing necrosis and apoptosis. This can destroy both the tumour-associated vasculature and the healthy vessels surrounding it, which leads to the reduction of oxygen and nutrient supply, and eventually indirect cell death due to hypoxia. PDT can also induce inflammatory responses against tumour cells. By inducing necrosis and inflammation, PDT activates both the innate and adaptive immunity. Consequently, T cells can circulate long term, providing lasting protection against the treated tumour. ² Different photosensitizers can be used for treatment, including 5-ALA, Temoporfin, Photofrin, Hypericin, or Talaporfin. For example, photofrin works by shrinking the tumours, such as a glioblastoma, and destroying tumour capillaries, especially at high light doses. This increases the death of the cancerous cells.⁵ 

Advantages of PDT

When it comes to treating cancer, photodynamic therapy (PDT) offers several benefits. Although first-generation photosensitizers may momentarily increase skin photosensitivity, which means the skin becomes hyper-reactive to light, they do not have long-term negative consequences when used properly. PDT improves patient comfort and recovery because it is less invasive than surgery and is typically done as an outpatient procedure. It increases the efficacy of treatment by damaging the tumour vasculature in addition to killing tumour cells. Its dual selectivity results from light irradiation being restricted to the therapy site and photosensitizers' propensity to accumulate preferentially in tumours. While intravenous injection permits adequate circulation to target tumours, topical use guarantees that photosensitizers only reach lesions. PDT is typically less expensive than other cancer therapies, rarely leaves scars, and can be repeated in the same spot.²

Limitations of PDT 

Photodynamic therapy has a number of limitations. One problem that can reduce treatment precision is photosensitizers' poor biodistribution following intravenous injection. The limited ability of light to penetrate and propagate through deep tissues is another challenge, which frequently leads to insufficient light supply to the tumour. Hypoxia (lack of oxygen) in the tumour environment can restrict PDT's ability to produce reactive oxygen species, which reduces the efficacy of treatment. Furthermore, PDT can only affect the tumour vasculature for a short while, which may be followed by vascular repair or angiogenesis. In a similar vein, partial or incomplete tumour tissue destruction may result in tumour recurrence. Lastly, PDT's long-term effectiveness may be diminished in certain situations when it is unable to stimulate antitumor immune responses adequately.⁶

Future directions 

For Glioblastoma (GBM), a highly aggressive and common brain tumour, PDT has been well investigated. However, the degree of therapeutic usefulness may be constrained by a number of biological and translational hurdles. Promising areas for future research should include near-infrared-based photoactivation for better tissue penetration, photoimmunotherapy (combining light therapy with immunotherapy), longitudinal administration (long-term plan with medicine given in repeated sessions), and nanoparticle-linked miRNA photosensitizers for a more focused anti-tumour strategy. Whatever the approach, the final translation to the clinical context must always be taken into account, keeping the patient's viewpoint at its core. https://pmc.ncbi.nlm.nih.gov/articles/PMC10341187/#sec6-cancers-15-03427.⁷

FAQs

What is photodynamic therapy (PDT), and how does it work?

 PDT is a treatment that combines a special light-sensitive drug (called a photosensitizer) with targeted light exposure. Once the drug is inside the body, it accumulates more in tumour cells than in healthy tissue. When doctors shine a specific wavelength of light on the tumour, the drug becomes active and triggers the production of molecules that damage and kill cancer cells.

How does PDT differ from traditional brain tumour treatments like surgery, radiation, and chemotherapy?

PDT does not require removing large sections of infected brain tissue, as is done in surgery. Furthermore, it does not circulate widely throughout the whole body, which does reduce its side effects like seen in chemotherapy. Radiation therapy requires repeated treatment, causing harmful long-term damage. However, PDT can be repeated multiple times without the occurrence of the harmful side effects.

What kinds of brain tumours can PDT be used for?

PDT has mostly been studied for aggressive tumours such as glioblastoma, as well as some lower-grade gliomas (a type of brain tumour that originates from glial cells) and brain metastases. It works best when the tumour is in a location that can be reached by light during or after surgery.

How effective is PDT in treating brain tumours?

PDT does not cure brain cancer on its own, but studies suggest it can slow tumour growth, help kill remaining cancer cells after surgery, and sometimes extend survival. Its effectiveness often depends on the tumour’s size, location, and the patient’s overall health.

What are the main advantages of PDT compared to other treatments?

It is highly targeted, so less healthy brain tissue is harmed. It can be repeated if a tumour comes back. It has fewer whole-body side effects. Furthermore, it activates the immune system against cancer.

Why can’t PDT be used for all brain tumours?

PDT only works when light can reach the tumour. Deep or widely spread tumours are harder to treat. The procedure also requires special equipment and training, which not all hospitals have.

Is PDT painful or difficult to recover from?

The treatment itself is not painful, since the light is delivered during or right after surgery under anaesthesia. Recovery is usually shorter compared to aggressive surgery or radiation, though patients must be careful about light exposure for several weeks.

Who is eligible for PDT in brain tumour treatment?

Eligibility depends on the type of tumour, its size, and whether it can be reached with light. Patients with tumours close to the surface or exposed during surgery are the most suitable candidates.

How long does the recovery period usually last after PDT?

 Physical recovery from the treatment is relatively quick, taking around a few days to a week. However, patients must avoid bright light exposure for at least 4–6 weeks to prevent skin or eye damage.