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Photodynamic Properties of Amphiphilic Derivatives of Aluminum Tetrasulfophthalocyanine ¶
Author(s) -
Allen Cynthia M.,
Langlois Réjean,
Sharman Wesley M.,
La Madeleine Carole,
Lier Johan E.
Publication year - 2002
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2002)0760208ppoado2.0.co2
Subject(s) - singlet oxygen , phototoxicity , chemistry , photodynamic therapy , porphyrin , photochemistry , singlet state , high performance liquid chromatography , medicinal chemistry , stereochemistry , organic chemistry , in vitro , oxygen , biochemistry , excited state , physics , nuclear physics
Photodynamic therapy (PDT) is a promising treatment modality that has recently been accepted in clinics as a curative or palliative therapy for cancer and other nonmalignant conditions. Phthalocyanines (Pc) are attractive photosensitizers for PDT because of their enhanced photophysical and photochemical properties. The overall charge and solubility of Pc play a major role in their potential usefulness for PDT. A series of amphiphilic derivatives of tetrasulfonated aluminum Pc (AlPcS 4 ) was prepared by substituting one of the four sulfonate groups with aliphatic side chains of 4, 8, 12 and 16 carbon atoms. The photodynamic properties of the derivatives were compared with those of AlPcS 4 and the adjacent disulfonated aluminum Pc. Parameters studied included reversed‐phase high‐performance liquid chromatography (HPLC) retention times, capacity to generate singlet oxygen ( 1 O 2 ), in vitro cell uptake and phototoxicity, as well as PDT response of transplantable EMT‐6 tumors in mice. The monomerized AlPcS 4 derivatives showed similar or higher capacities to generate 1 O 2 as compared with the parent AlPcS 4 as measured from relative l ‐tryptophan photooxidation yields. A549 cell uptake of the AlPcS 4 derivatives decreased in the following order: AlPcS 4 (C16) > AlPcS 4 (C12) > AlPcS 4 (C8) > AlPcS 4 (C4). Human low‐density lipoprotein at high concentrations (40 μg/mL) completely prevented uptake, whereas at 4 μg/mL uptake was decreased for the more lipophilic compounds and yet remained unaffected for the more hydrophilic dyes. Using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, A549 cell survival was assessed; it showed that photocytotoxic activity varied directly with the HPLC retention times, i.e. more hydrophilic compounds were less phototoxic. As 1 O 2 yields were similar for the four substituted AlPcS 4 derivatives, it was postulated that the increased cytotoxic activity was caused by enhanced subcellular localization as a result of the long aliphatic side chains. These amphiphilic compounds proved to be photodynamically potent against the EMT‐6 mouse mammary tumor model implanted in Balb/c mice. At dye doses of 0.2 μmol/kg and a fluence of 400 J/cm 2 complete tumor regression was observed with no morbidity. The substitution of AlPcS 4 with long aliphatic chains on the macrocycle greatly enhances its photodynamic efficacy both in vitro and in vivo.