Transition metal complexes as photosensitisers in one- and two-photon photodynamic therapy

Photodynamic therapy (PDT) exploits light-activated compounds for therapeutic use. It relies on a photosensitiser (PS) that is inactive in the absence of light. When irradiated, the PS absorbs light and is promoted to a higher energy, “excited” state (PS∗), which is either toxic to cells in itself or triggers formation of other species which are toxic to cells, and hence particular wavelengths of light can be used to induce light-dependent cell killing. In PDT occurring via the so-called type I and type II mechanisms, the PS∗ engages in energy transfer to dioxygen present in cells and tissues. This process generates highly reactive singlet oxygen (1O2) and/or other reactive oxygen species (ROS), which in turn cause damage in the immediate vicinity of the irradiation and ultimately can lead to cell death. Whilst the main focus of research for the last 50 years has been on organic molecules or porphyrins as sensitisers, there is now emerging interest in extending the use to transition metal (TM) complexes, which can display intense absorptions in the visible region, and many also possess high two-photon absorption cross-sections, enabling two-photon excitation with NIR light. As with any other type of photosensitiser, the issues to consider whilst designing a TM complex as a photosensitiser include cell permeability, efficient absorption of NIR light for deeper penetration, preferential affinity to cancer cells over healthy cells, targeted intracellular localisation and lack of side effects. This review summarises recent developments involving photosensitisers containing Ru(II), Os(II), Pt, Ir(III), and Re(I) ions, and the approaches used to address the above requirements. Several remarkable recent advances made in this area, including the first clinical trial of a metal complex as a photosensitiser, indicate the bright future of this class of compounds in PDT.