PHOTOSENSITIZING EFFICIENCIES, TUMOR‐ and CELLULAR UPTAKE OF DIFFERENT PHOTOSENSITIZING DRUGS RELEVANT FOR PHOTODYNAMIC THERAPY OF CANCER

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Abstract
Several parameters of the following dyes, all relevant as sensitizers for photochemotherapy of cancer, have been studied: Photofrin II (PII), hematoporphyrin (HP)‐di‐hexyl‐ether, HP‐di‐ethyl‐ether, tetra (3‐hydroxyphenyl) porphyrin, (3THPP), tetraphenyl porphine tetrasulphonate (TPPS4) aluminium phthalocyanine tetrasulfonate (A1PCTS), aluminium phthalocyanine (A1PC), chlorin e, (Chi e6) and merocyanine 540 (MC 540). The following parameters and features of these dyes were studied: (1) Tumor uptake in C3H mouse mammary carcinomas. (2) Skin/tumor concentration ratio in the same animal system. (3) Triton X‐114/H20 partition coefficients at different pH‐values. (4) Uptake of the dyes by human cells of the line NHIK 3025. (5) Relative fluorescence quantum yields of the dyes bound to cells. (6) Absorption‐, fluorescence‐excitation‐ and fluorescence‐emission spectra of the cell‐bound dyes. (7) Relative quantum yields for photoinactivation of cells after 18 h incubation with the dyes. (8) Relative quantum yields of photodegradation of the singlet oxygen trap 1,3‐diphenylisobenzofuran (DPBF) in cells after 18 h incubation with the dyes.The following main conclusions were drawn: (1) 3THPP was the best and most selective tumor localizer of the dyes tested, followed by AIPCTS, TPPS4, PII and Chi e.,. (2) The Triton X‐114/H20 partition coefficient of most of the dyes decreased with increasing pH. (3) The cellular uptake of the dyes (18 h incubation in medium with 3% serum) increased with increasing Triton X‐114/H20 partition coefficient. (4) HP‐di‐hexyl‐ether had the highest quantum yields both for photoinactivation of cells and degradation of cell‐bound DPBF, followed by the other lipophilic porphyrins and Chi e6. The water‐soluble dyes TPPS4and AIPCTS had quantum yields of the order of ten times lower than those of the lipophilic porphyrins. (5) There was a clear correlation between the quantum yields for cell‐inactivation and those for photodegradation of DPBF, suggesting that the same reactive photoinduced species is involved in both processes. This suggestion was strengthened by the observation that DPBF reduced the quantum yield of cell inactivation. Thus, all the tested dyes seem to actviaa type II process. (6) All of the dyes, even the water‐soluble TPPS4and AIPCTS, are aggregated in aqueous solutions, and the cells bind both monomers and aggregates. (7) A significant fraction of the cell‐bound dyes was located close to tryptophan‐containing proteins. (8) Cell‐bound Chi e,6had the highest fluorescence quantum yield of the dyes.

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