The photochemistry of sensitisers for photodynamic therapy

The preparation and photophysical properties of a number of water-soluble metallated phthalocyanines are described. These compounds have been shown to be effective photosensitizers for the destruction of tumours. The photophysics of various aluminium phthalocyanines of different degrees of sulphonation, from mono (S1) to tetra (S4); and of various disulphonated (S2) regioisomers was shown to be broadly similar, although the compounds varied greatly in terms of lip0 solubility, and phototoxicity. The effect of change of axial ligand, and of binding to the serum protein human serum albumin upon the photophysics of the dyes is also reported. btroduction Apart from radical surgery, the two major techniques used for the treatment of cancer are radiotherapy and chemotherapy. Whilst combatting tumour growth with some success, both methods can also induce disabling and life threatening side effects mainly because they destroy indiscriminately both normal and tumour tissue. Selective tumour destruction has thus become a major goal in oncology research. Photodynamic therapy (PDT) is a technique that uses light activated sensitisers, ie. compounds that are nontoxic until irradiated with light of an appropriate wavelength tuned to the absorption band of the sensitiser. Specific tumour targetting with PDT may be achieved firstly via using photosensitisers that accumulate preferentially in neoplastic tissue and secondly by confining and controlling the irradiation area using fibreoptically delivered laser light. Body tissue is relatively transparent in the red and near-infrared spectral regions with the consequence that PDT sensitisers absorbing at these longer wavelengths are able to produce a greater depth of tumour kill. The ideal properties of a photosensitiser are easily summarised, although the assessment of a sensitiser in these terms is not as straightforward as might be supposed because the heterogeneous nature of biological systems can profoundly affect the properties. Ideally, a sensitiser should be red or near infrared light absorbing; non-toxic, with low skin photosensitising potency; selectively retained in tumours relative to normal adjacent tissue; an efficient generator of cytotoxic species, usually singlet oxygen; fluorescent, for visualisation; of defined chemical composition, and preferably water soluble, although with use of liposome delivery systems, the last is not essential. The sequence of events in PDT are shown in Fig. 1, from which it can be seen that complete establishment of the protocol requires wider study of biochemical and photochemical phenomena. Here we concentrate upon the photochemical, with the following questions in mind. 1) What structure efficacy correlates in ‘good’ sensitisers can be established? 2) What is the effect of protein binding upon photochemical pperties? 3) What is the photochemical mechanism of primary damage? 117