Specially trained task force helps advance photodynamic treatments As chemical compounds called tetrapyrrolic photosensitisers can help fight microbial infection and cancer, a multidisciplinary group has been specially trained to ensure these molecules achieve their potential. Food and Natural Resources © Alexander Raths/Shutterstock.com Tetrapyrroles are a class of active chemical compound, comprising four ring-structured smaller compounds known as pyrroles. Treatments exploit how these molecules interact with light and oxygen. However, challenges will have to be overcome before this therapy can be used more widely. “Tetrapyrroles are not very soluble, they are problematic when inside the body, their light absorption is not always medically optimum and they can be difficult to synthesise,” explains Stéphanie Lhez, coordinator of the POLYTHEA project, undertaken with the support of the Marie Skłodowska-Curie Actions programme. POLYTHEA was set up to maximise the interaction between photosensitisers and light, improve the targeting of cancer cells and bacteria, and visualise the active photosensitiser compound in vivo and in vitro. To achieve these aims, POLYTHEA trained a task force of young scientists in multidisciplinary techniques. So far the project has resulted in 40 published articles, including a special issue published in the ‘Journal of Porphyrins and Phthalocyanines’. Building a network of specialists When tetrapyrroles absorb visible light in the presence of oxygen, they can produce highly reactive chemicals called ‘reactive oxygen species’ (ROS). These in turn induce oxidation in biomolecules – such as nucleic acids, lipids and proteins – leading to cell death. This makes tetrapyrroles of great medical interest because it means that bacterial or cancerous cells could be targeted by photodynamic therapies which harness this process. But this field relies on specialists from a range of disciplines including: organic and physical chemistry; biology and microbiology; and photophysics and optics. “While one person cannot specialise in all those fields, they should be able to work across these domains and understand the requirements of each therapeutic component,” remarks Lhez from the University of Limoges, the project host. POLYTHEA trained 10 early-stage researchers from nine European countries, to work across two domains – chemistry and biology, or biology and photophysics, or chemistry and photophysics – while also receiving basic training in the third. The researchers were also seconded to non-academic partners, exposing them to industrial challenges and broadening their technical expertise. Proof of concept Amongst others solutions, the team developed a platform based on bio-sourced compounds such as cellulose, chitosan and lignin, especially able to deliver photosensitisers within biological media. Important organic chemistry work also undertaken increased the interaction of the photosensitisers with light, using infrared for example, to spark the excited state necessary to produce the ROS. New tetrapyrrolic compounds also identified and investigated could better target deep cancer cells. One such example is a porphyrin-cyanine dyad that exhibits interesting light interaction properties. Despite the COVID-19 pandemic, most of POLYTHEA’s researchers were able to fine-tune their therapeutic areas through in vitro experiments, with two realising in vivo visualisations. Preclinical studies were also conducted with mouse models which included looking at the impact of photosensitisers on melanoma and colon carcinoma cancer, as well as radiolabelled molecules as theranostic agents. “While COVID-19 curtailed some experiments, we still managed to increase the fundamental understanding of the molecular mechanisms underpinning photodynamic therapies. We also developed new synthetic pathways and bio-sourced materials making our systems more suitable for the human body,” adds Lhez. Above and beyond Tetrapyrrolic photosensitisers are already used in photodynamic therapy to treat cancer and skin diseases such as acne, as well as in photo-antimicrobial chemotherapy (PACT). Yet, with European photodynamic therapy research and training still fragmented, POLYTHEA’s multidisciplinary approach helps consolidate expertise within the field. “We strongly believe that our work will benefit research communities developing new therapies that are less invasive and with fewer side effects,” concludes Lhez. Keywords POLYTHEA, cancer, microbial, infection, tetrapyrroles, photosensitisers, compounds, light
