THE SUBCELLULAR-LOCALIZATION OF ZN(II) PHTHALOCYANINES AND THEIR REDISTRIBUTION ON EXPOSURE TO LIGHT

The development of second-generation photosensitizers to improve photo dynamic therapy (PDT) is an area of extensive research, Three such com pounds that have been synthesized in our group are polysubstituted Zn( II) phthalocyanines that differ in their overall net charge (one catio nic, one anionic and one neutral). The aim of this study was to charac terize the drugs in terms of their uptake, cell killing efficacy and s ubcellular localization in RIF-1 cells in vitro and to identify any po ssible structure/function relationships, The results show that the rel ative uptakes and cell killing efficacy of each of the drugs follows t he order cationic much greater than neutral > anionic. For the anionic and cationic drugs the initial subcellular localization was in the ly sosomes as determined by fluorescence microscopy. The neutral phthaloc yanine demonstrated a more diffuse localization characteristic of memb rane staining with some involvement of the Golgi apparatus in the peri nuclear area. Following light exposure the drugs rapidly relocalized t o different sites within the cell in a manner that was apparently char ge dependent and this relocalization was accompanied by an increase in the fluorescence associated with the drugs. This indicates that the p rimary sites of localization of these photosensitizers may not be as i mportant as their secondary sites in producing cell killing during PDT , especially as the fluorescence intensity increases on relocalization .