Uptake subcellular localization and phototoxicity of photosensitizing porphyrins

摘要

Cytotoxicity, uptake, intracellular location and phototoxicity were compared for the naturally occurring porphyrins uroporphyrin III (UP), coproporphyrin III (CP) and protoporphyrin IX (PP), as well as for tetra-, tri-, di- and monosulphonated meso-tetraphenyl porphyrins (TPPS$- n$/ with n equals 4, 3, 2a, 1) in cultivated endothelial cells from calf aorta (BKEz-7). In addition, the uptake of CP and PP in the chick chorioallantoic membrane (CAM) was studied after intravenous application. Hydrophilic porphyrins (UP, CP, TPPS$-4$/ and TPPS$-3$/) exhibit low cellular uptake as well as low cyto- and phototoxicity as compared with the more hydrophobic compounds. UP, CP, TPPS$-4$/ and TPPS$-3$/ were mainly located in lysosomes, whereas PP, TPPS$-2a$/ and TPPS$-1$/ were preferentially observed in the cytoplasm - supposed to be located in cellular membranes of organelles - and exhibited pronounced light-induced reactions. A rapid uptake by the CAM vasculature (5 min. - 30 min. after application) and some delayed uptake by the CAM matrix (30 min. - 6 h with a maximum at 60 min.) were measured for CP and PP.