title: A comparative study of the cellular uptake and photodynamic efficacy of three novel zinc phthalocyanines of differing charge.
abstract: Three novel substituted zinc (II) phthalocyanines (one anionic, one cationic and one neutral) were compared to two clinically used photosensitizers, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) and polyhematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Using the RIF-1 cell line, photodynamic efficacy was shown to be related to cellular uptake. The cationic phthalocyanine (PPC, pyridinium zinc [II] phthalocyanine) had improved activity over the other two phthalocyanines and slightly improved activity over PHP and m-THPC. The initial subcellular localization of each photosensitizer was dependent upon the hydrophobicity and plasma protein binding. The phthalocyanines had a punctate distribution indicative of lysosomes, whereas m-THPC and PHP had a more diffuse cytoplasmic localization. A relocalization of phthalocyanine fluorescence was observed in some cases following low-level light exposure, and this was charge dependent. The anionic phthalocyanine (TGly, tetraglycine zinc [II] phthalocyanine) relocalized to the nuclear area, the localization of the hydrophobic phthalocyanine (TDOPc, tetradioctylamine zinc [II] phthalocyanine) was unchanged, whereas the distribution of the cationic phthalocyanine (PPC) became more cytoplasmic. This suggests that relocalization following low-level irradiation is a critical factor governing efficacy, and a diffuse cytoplasmic distribution may be a determinant of good photodynamic activity.
authors.affiliation: Centre for Photobiology and Photodynamic Therapy, School of Biochemistry and Molecular Biology, University of Leeds, UK. s.b.brown@leeds.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Ball
authors.forename: S
authors.initials: S
authors.lastname: Mayhew
authors.forename: S R
authors.initials: SR
authors.lastname: Wood
authors.forename: J
authors.initials: J
authors.lastname: Griffiths
authors.forename: D I
authors.initials: DI
authors.lastname: Vernon
authors.forename: S B
authors.initials: SB
authors.lastname: Brown
mesh_terms: D000818:Animals; D002460:Cell Line; D004563:Electrochemistry; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D054833:Isoindoles; D051379:Mice; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000378:metabolism; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine