Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

New class of light activated anti-cancer and anti-microbial agents

Donal O'Shea, Pharmaceutical & Medicinal Chemistry. Keywords: cancer, pharmacy, pharmaceutical sciences & chemistry, photodynamic therapy (pdt), anti-cancer, anti-microbial.

Photodynamic therapy (PDT) is a unique treatment modality for a range of disease classes, both cancerous and non-cancerous, which uses low energy light in conjunction with a photosensitizer to effect specific cell death. My research has developed a totally new class of PDT agent, the BF2 chelated dibromotetraarylazadipyrromethenes. Optimised synthetic procedures have been developed to facilitate the generation of an array of specifically substituted derivatives to demonstrate how control of key therapeutic parameters such as wavelength of maximum absorbance and singlet oxygen generation can be achieved. Our lead compounds display nano-molar EC50 values across a broad spectrum of human cancer cell lines and excellent levels of tumour clearance in a pre-clinical in vivo efficacy study of human tumour bearing nude mice. In addition a new approach to achieving selectivity for photodynamic therapy based upon the reversible off/on switching of the key therapeutic property (singlet oxygen generation) of a supramolecular photonic therapeutic agent in response to an external microenvironment stimulus has been developed. Further work into this unique selectivity approach is on-going.

Mentors Donal O'Shea.