Aluminum sulphonated phthalocyanines as sensitizers for photodynamic therapy: Cellular uptake, phototoxicity and sensitizer targeting in human Leukemia cells

There is a need to improve the selectivity of photodynamic therapy for better targeting of tumor cells. This was achieved by the in vitro targeting of liposome-encapsulated chloroaluminum tetrasulfonated phthalocyanine to CCRF-CEM cells via the monoclonal antibody PM-81 by using a biotin-streptavidin sandwich binding method.; Non-targeted cytotoxicity of free and liposome-encapsulated chloroaluminum tetrasulfonated phthalocyanine (AlS{dollar}sb4{dollar}Pc) on human leukemia T cells (CEM) was examined. Liposome-encapsulated AlS{dollar}sb4{dollar}Pc was a more potent photosensitizing agent than the free drug. The phototoxicity of the liposome-encapsulated drug and free drug was proportional to the dose of both the sensitizer drug and light. Liposomes with the highest drug/lipid ratios were most potent than those with lower encapsulation.; Cellular uptake kinetics of free and liposome drug was examined and the effect of several factors determined. CEM cells accumulated free and liposome-encapsulated sensitizer drug in a dose- and temperature-dependent manner but saturation levels within cells was not achieved at 48 hours of exposure. Free drug uptake by cells was profoundly reduced by increasing concentrations of serum in the media; however, serum did not affect liposome drug incorporation into cells. Both free and liposome-encapsulated drugs apparently were endocytosed, because drug uptake that was highest at 37{dollar}spcirc{dollar}C was significantly reduced at 4{dollar}spcirc{dollar}C. Even at the latter temperature uptake was considerable, and perhaps can be explained on the basis of pinocytosis. In most cases, increasing drug uptake corresponded with greater cytotoxicity of the drug species.; PM-81 recognizes CD15, a marker expressed by CEM cells. Flow cytometric analysis indicated that CD15 expression was modulated by the phase of culture growth. The profile of markers on CEM cells was identified with a panel of monoclonal antibodies. Direct antigen-antibody interaction did not affect expression of CD15.; Liposome-encapsulated photosensitizer drug was targeted to CEM cells in vitro by using PM-81, and the biotin streptavidin system. Targeted liposomes were 6 times more potent than the non-targeted species, and 4 times more potent than the free drug, at an 8 fold lower drug concentration.; The results of this study may have implications for the ex-vivo purging of bone marrow to remove residual leukemic cells prior to autologous transplantation.