The subcellular localization of Zn(II) phthalocyanines and their redistribution on exposure to light

The development of second-generation photosensitizers to improve photodynamic therapy (PDT) is an area of extensive research. Three such compounds that have been synthesized in our group are polysubstituted Zn(II) phthalocyanines that differ in their overall net charge (one cationic, one anionic and one neutral). The aim of this study was to characterize the drugs in terms of their uptake, cell killing efficacy and subcellular localization in RIF-1 cells in vitro and to identify any possible structure/function relationships. The results show that the relative uptakes and cell killing efficacy of each of the drugs follows the order cationic > > neutral > anionic. For the anionic and cationic drugs the initial subcellular localization was in the lysosomes as determined by fluorescence microscopy. The neutral phthalocyanine demonstrated a more diffuse localization characteristic of membrane staining with some involvement of the Golgi apparatus in the perinuclear area. Following light exposure the drugs rapidly relocalized to different sites within the cell in a manner that was apparently charge dependent and this relocalization was accompanied by an increase in the fluorescence associated with the drugs. This indicates that the primary sites of localization of these photosensitizers may not be as important as their secondary sites in producing cell killing during PDT, especially as the fluorescence intensity increases on relocalization.