Abstract
Localised production of reactive oxygen species (ROS) is a defence strategy employed in both animal and plant systems in response to pathogens. However, the release of high levels of ROS also causes rapid, non-selective death of animal, plant and bacterial cells. Photodynamic therapy (PDT) exploits this by using photosensitisers that respond to specific wavelengths of light to generate large amounts of ROS in order to destroy diseased tissues. However, existing photosensitisers used in the clinic are far from being typical drug compounds due to their large molecular weight structures, and suffer from drawbacks including long biological half-life, high hydrophobicity, and poor targeting which leads to skin photosensitivity for weeks after treatment.
LightOx are developing highly fluorescent, ‘drug-like’, small molecules which cause rapid cell death when activated by UV-A/405 nm or corresponding two-photon absorption of near-IR (800 nm) light, ostensibly through the production of ROS exclusively in a cellular environment. These novel photosensitisers exhibit robust cytotoxic activity in a range of in vitro cellular assays, and the irradiation and subsequent destruction of a zebrafish embryo has exemplified the potential utility of this novel class of compound in a therapeutic context.
By applying novel chemical approaches and innovative molecular design, LightOx have established the means to attach our novel photosensitisers to proteins, peptides and small molecule drugs. These advances have enabled the development of a range of technologies including protein complexes that enable cellular selectivity, organelle-targeting probes for precise imaging, and novel dual-action photoactive chemotherapeutic drug molecules. Through these advances, and by harnessing the inherent advantages of this new class of organic PDT agent, LightOx are hoping to realise the rich potential that PDT approaches have for the treatment of a wide range of diseases which, to date, have been severely limited by the inadequate properties of existing photosensitisers.
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