A new generation of photosensitizers for photodynamic cancer therapy

Cancer remains one of the leading causes of premature death worldwide. The ageing global population is making cancer an increasingly serious public health challenge, bringing significant economic costs and therapeutic challenges. According to the World Health Organization, the number of people aged over 60 will reach 2 billion (22% of the global population) by 2050. This is why modern medicine is constantly seeking new, non-invasive cancer treatment methods that could serve as alternatives to chemotherapy, radiotherapy, or surgical procedures.

Photodynamic therapy (PDT) is considered one of the most promising approaches, as it is often associated with fewer side effects and a lower risk of requiring additional treatment. The method is based on the use of special molecules—photosensitizers—which, when activated by light, generate reactive oxygen species (ROS), highly reactive molecules capable of damaging and destroying cancer cells while limiting harm to healthy tissues. However, photodynamic therapy currently faces a significant limitation—its effective action requires oxygen, while tumours often develop in oxygen-deprived (hypoxic) environments. This makes conventional PDT less effective, particularly in the treatment of solid tumours. The project carried out by researchers from WUT and the Warsaw University of Life Sciences aims to overcome this limitation by developing a new generation of photosensitizers based on heavy-atom-free BODIPY-type dyes, which can be designed at the molecular level.

WUT researchers will develop a new generation of photosensitizers for photodynamic cancer therapy

The uniqueness of this approach lies in the use of BODIPY systems composed of two complementary components—a boron-containing unit and a BODIPY core. The transfer of electrons between these molecular partners under red light irradiation leads to the generation of reactive oxygen species. Unlike conventional systems, these compounds do not require the use of toxic heavy elements. The developed molecules generate free radicals—a type of ROS whose production is significantly less dependent on oxygen concentration. Additionally, these systems enable the attachment of targeting groups that direct the molecules specifically to cancer cells and even to specific organelles, maximizing therapeutic efficacy while minimizing damage to healthy tissues.

As part of the project, the researchers plan to systematically investigate how different structural elements influence ROS generation, with particular emphasis on free radicals. A library of new compounds will be created, and their properties will be thoroughly characterized. This will be followed by biological testing, including studies using three-dimensional cancer cultures that mimic the actual conditions found in tumours.

“Precise photochemistry using new light-sensitive molecules paves the way for more effective and safer cancer treatment,” says Krzysztof Durka, PhD, the project leader.

The project addresses the key challenges currently facing photodynamic therapy. It aims to increase treatment efficacy under low-oxygen conditions by generating ROS radicals that are less dependent on the presence of oxygen, alongside singlet oxygen. At the same time, the use of red light is expected to improve tissue penetration, while the incorporation of groups that target molecules to cancer cells will increase the selectivity of the treatment. An important element of the project is also the safety resulting from the elimination of heavy elements that may cause toxicity, as well as the practicality of the solution, based on simple chemistry that enables the scaling up of synthesis for future clinical applications.

The project “Regulation of reactive oxygen species photogeneration through structural modulation of BODIPY photosensitizers for anticancer photodynamic therapy” has received funding under the OPUS 30 call.