Cancer is among the leading causes of death worldwide. In the UK, incidence rates of cancer are projected only to rise over the years. A variety of therapies have been utilised over the years to combat this disease, each with varying efficacies. While our ability to quickly diagnose and effectively treat cancer has improved, progress in the field is still necessary to reduce the side effects and improve the effectiveness of cancer treatment.
Photodynamic therapy (PDT) is a developing cancer treatment option that utilises light-sensitive drugs called photosensitisers to destroy cancer cells. When exposed to specific wavelengths of light, these photosensitisers become activated and trigger reactions that kill the cells they are localised in. While PDT offers great potential as a selective and minimally invasive cancer treatment option, several drawbacks still limit the wider applicability of PDT. For instance, PDT is limited by how deeply light can penetrate tissues. PDT is also currently unable to address cancers that have spread throughout the body. Furthermore, side effects such as high sensitivity to light has been reported for patients being treated with PDT.
Research efforts aimed at advancing PDT mainly focus on searching for more effective photosensitisers and better methods for their delivery (or light delivery) into the patient's body. In this research paper published in The Journal of Physical Chemistry B, Prof. Susan Quinn and PhD student Mark Stitch from University College Dublin collaborated with Rosie Sanders, Igor Sazanovich, Michael Towrie and Stan Botchway from the CLF to investigate how two new photosensitisers interact with DNA. Their research contributes to the search for better photosensitisers by helping us better understand how they work.
The photosensitisers under investigation are two ruthenium polypyridyl complexes with the same number and type of atoms but slightly different structures. While complex I has a DNA-binding site with a linear structural component (dppn ligand), complex II has a DNA-binding site with a hooked structural component (pdppz ligand). Using the time-resolved infrared (TRIR) spectroscopy apparatus stationed at the CLF's ULTRA facility, the team found that surprisingly, this slight difference in structure led to each having a significantly different mechanism of action on DNA. Their studies revealed that complex I most likely causes DNA damage by the generation of a chemically reactive excited-state oxygen molecule (singlet oxygen), while complex II damages DNA through direct electron transfer. They also found that complex II causes DNA damage much more rapidly than complex I.
Through their research, the authors highlighted the significant impact molecular structure can have on the action of photosensitisers. This is valuable knowledge to keep in mind as we continue looking for new photosensitisers to advance PDT. Given that both complexes are able to be delivered relatively effectively into cells, they show promise as a candidate for future PDT research and trials.
See the published paper here.
