Novel transition metal complexes for use as photosensitizers in photodynamic therapy

Herein, the exploration of a range of novel TM complexes for use as PS in the PDT of cancer is reported. Novel small-molecule TM complexes of Pt(II), Os(II) and Ir(III) metal centres were explored. Their photophysical characteristics, such as wavelength of activation and singlet oxygen yields, were assessed for suitability as PS before cellular uptake and toxicity in the dark was determined. Compounds showing favourable cellular uptake and toxicity upon initial screening were explored further. An iridium complex (IrNew) emerged as the most promising PS candidate showing high PS activity and low dark toxicity in a number of cancer cell lines. The mitochondrial localisation and apoptotic mode of cell death of IrNew was determined. With a high photo-toxicity index (up to > 555) at low light doses (3.6 J cm-2) the reported compound is a promising candidate but the need for relatively short wavelength light (405 nm) to activate the compound would severely limit its clinical use. As such alternative modes of activation were explored. An alternative to one-photon activation in PDT is two-photon activation allowing PS activation in the NIR. IrNew, in combination with NIR light (λexc = 760 nm), led photo-induced cell death in cell monolayers (HeLa) clearly demonstrating the potential of IrNew as a two-photon activated PS. The use of 3D oral cancer models as a tool for investigation of tissue effects in PDT were developed for the first time. While two- photon activation offers PS activation in the NIR, the requirement for high power lasers has hindered its clinical application. As an alternative, lanthanide upconverting nanoparticles which can transform two photons of near-infrared (NIR) light into a photon of UV/Vis light to activate the photosensitizer were successfully synthesised. These particles represent potential future treatment modality in the development of continuous wave NIR PDT.