In vitro and in vivo studies of new cationic Zn(II)-benzonaphthoporphyrazines as photosensitizers for PDT
Abstract
Four recently synthesized cationic zinc(II)-benzonaphthaporphyrazines 1–4 were studied in vitro and in vivo for their photodynamic therapy (PDT) effectivity. The photophysical measurements showed that in solution and in Cremophor 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 culture. The dark toxicity examinations on invasive human bladder carcinoma cell line EJ did not show any traces of toxicity. The investigations connected with the detection of their phototoxic capacity on the same cell line demonstrated very promising results especially with photosensitizers 3 and 4. The in vivo studies with these two compounds demonstrating high cell-phototoxic effect were carried out against Lewis lung carcinoma in mice after incorporation in Cremophor micelles. The excitation was done at the respective maximum absorption wavelength for each of the sensitizers at a fluence rate of 380 mW cm-2 and a fluence of 360 J cm-2. The phototherapeutic effect was evaluated through macroscopic observations (tumour growth delay) and by electron microscopy detection. According to these approaches the best effect (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.
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