Combinational sensitization of Leishmania with uroporphyrin and aluminum phthalocyanine synergistically enhances their photodynamic inactivation in vitro and in vivo.
Combinational sensitization of Leishmania with uroporphyrin and aluminum phthalocyanine synergistically enhances their photodynamic inactivation in vitro and in vivo.
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DOI：
10.1111/j.1751-1097.2012.01076.x
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发表时间：
2012-05
影响因子：
3.3
通讯作者：
Chang KP
中科院分区：
文献类型：
--
作者：
Dutta S;Waki K;Chang KP
利什曼原虫先前被证明经历光解时，其转基因突变体被诱导内源性积累细胞质尿卟啉或当加载外源性与铝酞菁氯化物。这里报告了两者的组合使用，这使得利什曼原虫更容易光解。荧光显微镜下的细胞与两种光敏剂本地化他们到不同的亚细胞网站。预先暴露的利什曼原虫都协同敏化它们的光解作为细胞外前鞭毛体和细胞内无鞭毛体在体外感染的巨噬细胞时，在特定的波长照射，以激发各自的光敏剂生产的活性氧。两个利什曼原虫阶段完全失去了他们的活力时，双重光敏最佳和低强度照明，宿主细胞被留下毫发无损。用光灭活的利什曼原虫接种小鼠没有产生病变，在为期8周的观察期间，这些病变总是在对照组中发生。用两种光敏剂预处理利什曼原虫使这些细胞易于通过白色光照射从耳真皮清除。结果表明，双重光敏化的协同活性提高了光动力治疗的疗效和安全性，特别是利什曼原虫。
Leishmania were previously shown to undergo photolysis when their transgenic mutants were induced endogenously to accumulate cytoplasmic uroporphyrin or when loaded exogenously with aluminum phthalocyanine chloride. A combinational use of both is reported here, which renders Leishmania far more susceptible to photolysis. Fluorescence microscopy of cells loaded with the two photosensitizers localized them to different subcellular sites. Pre-exposure of Leishmania to both synergistically sensitized them for photolysis as extracellular promastigotes and as intracellular amastigotes in infected macrophages in vitro when illuminated at specific wavelengths to excite the respective photosensitizers for production of reactive oxygen species. Both Leishmania stages lost their viability completely when doubly photosensitized optimally and illuminated at low intensity, the host cells being left unscathed. Inoculation of mice with photo-inactivated Leishmania produced no lesions, which invariably developed in the control groups during a period of observations for eight weeks. Pre-treatment of Leishmania with both photosensitizers rendered these cells susceptible to clearance from the ear dermis by white light illumination. The results suggest that double photosensitization for synergistic activity enhances the efficacy and safety of photodynamic therapy in general and for Leishmania in particular.
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影响因子：
9.7
作者：
CANTI, G;LATTUADA, D;VALENTINI, G
通讯作者：
VALENTINI, G
影响因子：
3.4
作者：
CASTRO, DJ;SAXTON, RE;SOUDANT, J
通讯作者：
SOUDANT, J
影响因子：
3.7
作者：
Dutta S;Ongarora BG;Li H;Vicente Mda G;Kolli BK;Chang KP
通讯作者：
Chang KP
影响因子：
2.1
作者：
Dutta, Sujoy;Furuyama, Kazumichi;Chang, Kwang-Poo
通讯作者：
Chang, Kwang-Poo
影响因子：
3.3
作者：
Zhao B;He YY
通讯作者：
He YY