Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT.

Porphyrinic molecules have a unique theranostic role in disease therapy; they have been used to image, detect and treat different forms of diseased tissue including age-related macular degeneration and a number of different cancer types. Current focus is on the clinical imaging of tumour tissue; targeted delivery of photosensitisers and the potential of photosensitisers in multimodal biomedical theranostic nanoplatforms. The roles of porphyrinic molecules in imaging and pdt, along with research into improving their selective uptake in diseased tissue and their utility in theranostic applications are highlighted in this Review.

Photodynamic sensitizers are drugs activated by light of a specific wavelength and are used in the photodynamic therapy (PDT) of certain diseases. Second-and third-generation photosensitizers with improved PDT properties are now under investigation. In this issue of the British Journal of Pharmacology, Leung et al. have described the synthesis and investigation of a second-generation photosensitizer (BAM-SiPc) targeted towards the cells of HepG2 and HT29 tumours. BAM-SiPc is selectively functionalized with bis-amino groups and has demonstrated potent PDT activity in a small animal model. However, it also exhibited non-selective distribution and accumulation in multiple animal (small mouse) organs and tissue. These issues highlight the importance and need for good biodistribution and localization properties for an efficacious photosensitizer. The lack of tumour specificity may have a significant impact on the potential BAM-SiPc has in clinical PDT.

Reactive oxygen species (ROS) have for some time been implicated in the onset and progression of medical conditions including cancer, ageing, heart disease and Alzheimer's disease. Recently, it has been postulated that ROS play a much more subtle role in intracellular signalling mechanisms as second messengers. Given the importance of these species in influencing cellular processes, it is surprising that tools for studying intracellular levels of ROS are extremely limited and devices for studying the cells' response to internally generated ROS are virtually non-existent. In order to study the response of cells to intracellular ROS we have designed a nano-scale device that can both generate ROS and simultaneously monitor the cells' reaction as a function of changes in the important signalling ion, calcium. Here we report the synthesis, characterisation, and calibration of a new ROS nano-probe and demonstrate its ability to detect cellular response to elevated levels of intracellular ROS.