In vitro and in vivo studies of new cationic Zn(II)benzonaphthoporphyrazines as photosensitizers for PDT

Four recently synthesized cationic zinc(II)-benzonaphthaporphyrazines 1-4 w ere studied in vitro and in vivo for their photodynamic therapy (PDT) effec tivity. The photophysical measurements showed that in solution and in Cremo phor micelles all examined compounds exhibit very high absorption intensity in the spectral range between 680 to 750 nm. The fluorescence emission for 3 and 4 was very well expressed in different media, as well as in cell cul ture. The dark toxicity examinations on invasive human bladder carcinoma ce ll line EJ did not show any traces of toxicity. The investigations connecte d with the detection of their phototoxic capacity on the same cell line dem onstrated very promising results especially with photosensitizers 3 and 4. The in vivo studies with these two compounds demonstrating high cell-photot oxic effect were carried out against Lewis lung carcinoma in mice after inc orporation in Cremophor micelles. The excitation was done at the respective maximum absorption wavelength for each of the sensitizers at a fluence rat e of 380 mW cm(-2) and a fluence of 360 J cm(-2.) The phototherapeutic effe ct was evaluated through macroscopic observations (tumour growth delay) and by electron microscopy detection. According to these approaches the best e ffect (including tumour destroyment) was detected after PDT treatment with the cationic tribenzonaphthoporphyrazinato-zinc(II) 3. Typical features of random, but not of programmed, cell death necrosis were observed. Copyright (C) 2001 John Wiley & Sons, Ltd.