Gottlieb P, Shen L G, Chimezie E, Bahng S, Kenney M E, Horowitz B, Ben-Hur E
Lindsley F. Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA.
Photochem Photobiol. 1995 Nov;62(5):869-74. doi: 10.1111/j.1751-1097.1995.tb09149.x.
Three phthalocyanine dyes HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), HOSiPcOSi(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 (> or = 5 log10) was found to occur with 2 microM Pc 4 after irradiation with red light (> 600 nm) at a fluence of 7.5 J/cm2, while with RBCC as the medium, a complete loss was found to occur at a fluence of 15 J/cm2. Even without illumination, Pc 4 at 2 microM 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 related 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.
评估了三种酞菁染料,即HOSiPcOSi(CH3)2(CH2)3N(CH3)2(Pc 4)、HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I-(Pc 5)和氢氧化四磺基铝酞菁(AlOHPcS4)在新鲜冷冻血浆(FFP)和红细胞浓缩液(RBCC)中使克氏锥虫无鞭毛体形式失活的能力。发现化合物Pc 4在杀死克氏锥虫方面非常有效,Pc 5效果较差,而AlOHPcS4无效。以FFP为介质,在用波长>600 nm的红光以7.5 J/cm2的光通量照射后,发现2 microM的Pc 4能使体外寄生虫感染性完全丧失(≥5 log10),而以RBCC为介质时,在15 J/cm2的光通量下会出现完全丧失。即使不光照,2 microM的Pc 4在30分钟内也能杀死FFP中约3.7 - 4.1 log10的克氏锥虫。观察到的各种酞菁对克氏锥虫杀伤的差异可能与结合差异有关;Pc 4与寄生虫的结合量约为Pc 5的两倍。对处理过的寄生虫的超微结构分析表明,线粒体是这种光动力治疗的主要靶点。数据表明,Pc 4与红光照射相结合可用于从用于输血的血液成分中消除血源性病原体克氏锥虫。Pc 4在黑暗中对克氏锥虫的灭活表明其可能具有治疗应用价值。