Basic reaction mechanisms of hydrophilic and lipophilic photosensitisers in photodynamic tumour treatment

SummaryThe efficiency of photodynamic therapy is dependent on the localisation of a photosensitiser in the target tissue and inside cells. Small lipophilic molecules penetrate the plasma membrane by diffusion and may be retained there. An inhomogeneous subcellular distribution in extranuclear granules is observed for most of the hydrophilic photosensitisers which are taken up by pinocytosis and for lipophilic dyes, which are administered via the LDL-endocytotic pathway. Biodynamics are different for lipophilic and hydrophilic drugs. A complex cellular and subcellular relocalisation is observed during varying incubation times and during the light-induced process. Using the chorioallantoic membrane of fertilised eggs as a substrate for tumour cells, the pharmacodynamics of sensitisers can easily be followed with confocal laser scanning-microscopy. With confocal detection it is possible to distinguish between endothelial cells of the vessel wall, the lumen of the vessels and tumour cells. Lipophilic drugs were found to accumulate in high amounts in the vessels, especially in the endothelial cells, whereas hydrophilic drugs are cleared from the plasma more quickly and accumulate in the tumour cells after a short incubation time. The light-induced subcellular dynamics were also found to be different for lipophilic and hydrophilic photosensitisers. Whereas photobleaching was observed for lipophilic drugs in correlation with necrotic processes, the fluorescence of hydrophilic sensitisers exhibited a sigmoid behavior, in correspondence with transient nuclear calcium changes, which may have some implications for apoptotic processes.