A comparative study of the cellular uptake and photodynamic efficacy of three novel zinc phthalocyanines of differing charge

Three novel substituted zinc phthalocyanines (one anionic, one cationic and one neutral) were compared to two clinically used photosensitizers, 5,10,1 5,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) and polyhematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Using the RIF-1 cell li ne,photodynamic efficacy was shown to be related to cellular uptake. The ca tionic phthalocyanine (PPC, pyridinium zinc [II] phthalocyanine) had improv ed activity over the other two phthalocyanines and slightly improved activi ty over PHP and m-THC. The initial subcellular localization of each photose nsitizer was dependent upon the hydrophobicity and plasma protein binding. The phthalocyanines had a punctate distribution indicative of lysosomes, wh ereas m-THPC and PW had a more diffuse cytoplasmic localization, A relocali zation of phthalocyanine fluorescence was observed in some cases following low-level light exposure, and this was charge dependent. The anionic phthal ocyanine (TGly, tetraglycine zinc Cn] phthalocyanine) relocalized to the nu clear area, the localization of the hydrophobic phthalocyanine (TDOPc, tetr adioctylamine zinc [II] phthalocyanine) was unchanged, whereas the distribu tion of the cationic phthalocyanine (PPC) became more cytoplasmic, This sug gests that relocalization following low-level irradiation is a critical fac tor governing efficacy, and a diffuse cytoplasmic distribution may be a det erminant of good photodynamic activity.