SULFOPHTHALOCYANINES FOR PHOTODYNAMIC INACTIVATION OF VIRUSES IN BLOOD PRODUCTS - EFFECT OF STRUCTURAL MODIFICATIONS

Transmission of infectious diseases through blood transfusions is well known. Ultraviolet irradiation, solvents and detergents provide a mea ns of sterilizing noncellular blood components. However these harsh me thods are not applicable to cellular blood products. Recently, attempt s have been made to sterilize biological fluids using photodynamic tre atment and phthalocyanine (Pc) dyes have been advanced as photosensiti zers for this purpose. We have evaluated a series of water-soluble Pc, chelated with different central metal ions, substituted to different degrees with sulfonato and t-butyl groups, for their effectiveness to reduce virus infectivity in red blood cell suspensions. Vaccinia virus cytopathogenicity was determined by endpoint serial dilutions in the CV-1 cell line. Anti-viral activity increased with the central metal i on in the following order: Ga(III) < Al(III) < Zn(II), and varied inve rsely with the degree of sulfonation. Furthermore, addition of a t-but yl group onto the trisulfonated dyes (PcS(3)[t-Bu]) resulted in a 5-40 -fold increase in anti-viral potency, suggesting that amphiphilicity e nhances the photodynamic activity of the dye. Strong anti-viral photos ensitizing properties cannot be the sole selection criterion. Of equal importance is the preservation of blood component integrity. Accordin gly, the photohemolytic activity of the dyes was evaluated using the r ate of hemolysis as a parameter and a toxicity index was defined. Amon g the most active dyes, the AlPcS(3)(t-Bu) complex exhibited the most favorable anti-viral properties combined with a low toxicity index. Ou r results suggest that trisulfophthalocyanines, bearing an additional t-butyl group to enhance amphiphilicity, are particularly promising dy es for photodynamic blood sterilization.