INACTIVATION OF Trypanosoma cruzi TRYPOMASTIGOTE FORMS IN BLOOD COMPONENTS BY PHOTODYNAMIC TREATMENT WITH PHTHALOCYANINES |
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| Authors: | Paul Gottlieb Li-Gang Shen Eleanor Chimezie Soon Bahng Malcolm E Kenney Bernard Horowitz Ehud Ben-Hur |
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| Institution: | The Lindsley F. Kimball Research Institute of the New York Blood Center, 310 East 67th Street, New York, NY 10021, USA;Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA |
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| Abstract: | Abstract— -Three phthalocyanine dyes HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), HOSiPc-OSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) and aluminum tetrasulfophthalocyanine hydroxide (AlOHPcS4) were evaluated for their ability to inactivate the trypomastigote form of Trypanosoma cruzi in fresh frozen plasma (FFP) and red blood cell concentrates (RBCC). The compound Pc 4 was found to be highly effective in killing T. cruzi, Pc 5 less effective and AlOHPcS4 ineffective. With FFP as the medium, a complete loss of parasite infectivity in vitro (≥5 log10) was found to occur with 2 μ M Pc 4 after irradiation with red light (>600 nm) at a fiuence of 7.5 J/cm2, while with RBCC as the medium, a complete loss was found to occur at a fiuence of 15 J/cm2. Even without illumination, Pc 4 at 2 μ M also killed about 3.7-4.1 log10 of T. cruzi in FFP during 30 min. Observed differences in T. cruzi killing by the various phthalocyanines may relate to differences in binding; Pc 4 binds to the parasites about twice as much as Pc 5. Ultrastructural analysis of treated parasites suggests that mitochondria are a primary target of this photodynamic treatment. The data indicate that Pc 4 combined with exposure to red light could be used to eliminate bloodborne T. cruzi parasites from blood components intended for transfusion. The inactivation of T. cruzi by Pc 4 in the dark suggests a possible therapeutic application. |
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