Structure‐Photodynamic Activity Relationships of a Series of 4‐Substituted Zinc Phthalocyanines

Abstract

Radioiodinated zinc phthalocyanine including [125I]ZnPcI4 and differently sulfonated [65Zn]ZnPcS (ZnPcS4, ZnPcS3, ZnPcS2 and ZnPcS1.75, a mixture of adjacent di and 25% mono) were prepared in order to study cell uptake and release kinetics in EMT-6 cells. The same compounds were evaluated for their in vitro phototoxicity and the biological parameters were compared to partition coefficients to arrive at quantitative structure-activity relationships (QSAR). At 1 microM in 1% serum, at 37 degrees C, all dyes showed rapid cell uptake during the first hour followed by a slow accumulation phase. After 24 h, the highest cellular concentration was observed with the lipophilic ZnPcI4, followed by the amphiphilic ZnPcS2 and ZnPcS1.75. The hydrophilic ZnPcS4 and ZnPcS3 showed lower uptake. Dye release from dye-loaded cells during incubation in dye-free medium could reach up to 60% and was shown to depend mainly on the amount of drug incorporated rather than the type of compound. These results suggest that care should be taken in interpreting dye toxicity data, which involve in vitro cell manipulations in dye-free medium, particularly during in vitro-in vivo protocols. The EMT-6 cell survival after 1 h or 24 h incubation with 1 microM dye in 1% serum followed by exposure to red light was assessed by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium bromide (MTT) assay. Photocytotoxicities correlated inversely with the tendencies of the dyes to aggregate. Increased dye uptake by the cells also correlated with their activities, except for the lipophilic ZnPcI4, which showed the highest cell uptake but little phototoxicity. The QSAR between phototoxicity and the log of the partition coefficients (phosphate-buffered saline and n-octanol) gave a parabola with optimal partition values corresponding to the adjacent sulfonated ZnPcS2.

Water-soluble aluminium phthalocyanine–polymer conjugates for PDT: photodynamic activities and pharmacokinetics in tumour-bearing mice

“…An inverse relationship was related between the degree of substitution by sulphonato groups of MePc and their hydrophobicity and photodynamic activities, both at the cellular level and in tumour-bearing mice (Brasseur et al, 1987(Brasseur et al, , 1988Paquette et al, 1988;Berg et al, 1989;Chan et al, 1990Chan et al, , 1991Margaron et al, 1996a). The potential of the water-soluble aluminium sulphophthalocyanine (AlPcS) to generate activated oxygen species (Sharman et al, 1999) and to induce a photodynamic response in vivo has been widely evaluated, and a mixture of AlPcS bearing 2-4 sulphonato groups per Pc (Photosense) is used extensively and successfully in clinical PDT in Russia (Zharkova et al, 1994).…”

Optimum modality for photodynamic therapy of tumors: gels containing liposomes with hydrophobic photosensitizers

“…1) also possess an advantage in that they have a high extinction coefficient, of 4100,000 M À1 cm À1 with absorption maxima in the 670-780-nm range [Margarone et al, 1996;Boyle et al, 1992;Alexandratou et al, 2005;Fabris et al, 2006]. An even higher extinction coefficient is natural for naphthalocyanines [Cuomo et al, 1990;Nyman and Hynninen, 2004].…”

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…It has been proven by several groups that amphiphilic molecules versus hydrophilic and hydrophobic molecules show a greater degree of activity and can localize at the interface of hydrophobic-hydrophilic membranes [339,340] . Amphiphilicity can also effect the aggregation of PSs and in turn affect the photophysical properties of a PS [12] .…”