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.

e.g. rose bengal and the hypericins, have also been omitted to allow meaningful comparisons to be made between difPhotodynamic therapy (PDT) has, during the last quarter ferent compounds. As the intracellular distribution of phocentury, into a fully fledged lieid tosensitizers to organelles and other subcellular structures with its own association, the International Photodynamic can have a large effect on PDT efficacy, a section will be Association ( P A ) and regular conferences devoted solely devoted to this topic. to this topic. Recent approval of the first PDT sensitizer, Photofrinm (porfimer sodium), by health boards in Canada, Japan, the Netherlands and United States for use against certain types of solid tumors represents, perhaps, the single most significant indicator of the progress of PDT from a laboratory research concept to clinical reality.The approval of Photofrinm will undoubtedly encourage the accelerated development of second-generation photosensitizers, which have recently been the subject of intense study. Many of these second-generation drugs show significant differences, when compared to Photofrinm, in terms of treatment times postinjection, light doses and drug doses required for optimal results. These differences can ultimately be attributed to variations in either the quantum efficiency of the photosensitizer in s h , which is in turn affected by aggregation state, localized concentration of endogenous quenchers and primary photophysics of the dye, or the intratumoral and intracellular localization of the photosensitizer at the time of activation with light. The purpose of this review is to bring together data relating to the biodistribution and pharmacokinetics of second-generation sensitizers and attempt to correlate this with structural and electronic features of these molecules. As this requires a clear knowledge of photosensitizer structure, only chemically well-characterized compounds are included, e.g. PhotofrinB and crude sulfonated phthalocyanines have been excluded as they are known to be complex mixtures. Nonporphyrin-based photosensitizers,

Heavy atom-free BODIPY-anthracene dyads (BADs) generate locally excited triplet states by way of photoinduced electron transfer (PeT), followed by recombination of the resulting charge-separated states (CSS). Subsequent quenching of the triplet states by molecular oxygen produces singlet oxygen (O2), which reacts with the anthracene moiety yielding highly fluorescent species. The steric demand of the alkyl substituents in the BODIPY subunit defines the site of O addition. Novel bis- and tetraepoxides and bicyclic acetal products, arising from rearrangements of anthracene endoperoxides were isolated and characterized. O generation by BADs in living cells enables visualization of the dyads distribution, promising new imaging applications.