Variation in Photodynamic Efficacy during the Cellular Uptake of Two Phthalocyanine Photosensitizers

A decrease in the efficacy of photodynamic therapy (PDT) with phthalocyanine photosensitizers was observed for lymphoblastic murine and human cell lines as the time between the addition of the photosensitizer, aluminum phthalocyanine (AlPc), to the culture medium and exposure to light was increased from 4 h to 18 h. The total intracellular concentration of photosensitizer did not decrease significantly during this 18 h interval. For the murine cell lines, the maximum cytotoxic and mutagenic effects were observed when the time between addition of the photosensitizer and irradiation was between 1 and 4 h. The time course of the variations in efficacy did not vary greatly from one murine cell line to another, even though the cell lines differ markedly in the extent of their cytotoxic and mutagenic response. The time course of the variation was similar for cytotoxicity and mutagenicity, as well as for the induction of DNA fragmentation. The human lymphoblastic cell line, WTK1, showed less variation in survival and mutability with time than did the murine cell lines. With Pc 4 (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) as the photosensitizer, the photocytotoxicity for murine L5178Y (LY)-Sl cells did not change significantly as the time between addition of Pc 4 and irradiation was increased from 2 to 18 h. However, the mutagenicity decreased by a factor of three during this interval. The mutagenicity of PDT with Pc 4 was much less in LY-Sl cells than that with AlPc. The results suggest that the variation in the efficacy observed for AIPc-induced photocytotoxicity is caused by changes in the intracellular distribution and/or the aggregation of the photosensitizer with time after its addition.