Photophysics and photocytotoxicity of 2,9(10),16(17),22(25)-tetrakis[(2-N,N-dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II) incorporated into liposomes

LOPEZ ZEBALLOS N.; MARINO V.J.; GARCIA VIOR M.C.; ROGUIN, L. P; AWRUCH J; DICELIO L.E.

Mendoza

Conferencia; 21st Inter-American Photochemical Society (I-APS) Conference; 2011

Liposomes with various lipid compositions are widely used as carriers systems for water- insoluble compounds in experimental studies and clinical trials. The extreme hydrophobicity of phthalocyanines makes necessary the use of specific carriers for their delivery into biological systems for photodynamic therapy (PDT). The presence of cholesterol in the liposome formulations enhance their mechanical stability, avoiding structural disintegration in blood. 2,9(10),16(17),22(25)-tetrakis[(2-N,N-dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II) (ZnPc) was incorporated into two different liposome formulations of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, with (D1) and without cholesterol (D2). Both systems were studied in order to evaluate the photophysical properties, as well as their photocytotoxicity using human nasopharynx KB carcinoma cells. The average diameter of liposomes varied from 49.70 to 52.00 nm. The polydispersity (i.e., the measurement of size heterogeneity) for the size distribution of liposomal formulations ranged from ± 0.088 to ± 0.35. Spectroscopic characterization of free and incorporated into liposomes ZnPc absorption and emission spectra were used to establish the incorporation of the dye into liposomal formulations. ZnPc into D1 and D2 formulations show a band at 648.5 and 642.5 nm respectively corresponding to dimer ZnPc. The relative fluorescence quantum yields (ΦF) are 7,2 x 10-3 and 8,3 x 10-3, and the singlet oxygen quantum yield production (ΦΔ) values are 0,34 and 0,42 for D1 and D2 respectively. The effect of different concentrations of phthalocyanines on KB cell survival was evaluated in the dark and upon exposure to a light dose of 4.7 J cm-2, between 630-700 nm during 40 minutes. No dark cytotoxicity was observed when cells were exposed up to a 100 μg/ mL concentration of liposomes. On the contrary, when cells were treated with ZnPc incorporated into D1 and D2, cell viability diminished in a concentration-dependent manner, the 50% inhibition of cell proliferation (IC50) being obtained at a concentration less than 1 μM.In conclusion, ZnPc liposomes have a good cytotoxic behavior, in spite of dye dimerization.