Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle–polyvinylpyrrolidone-[meglumine antimoniate (Glucantime®)]) nanocomposite during Leishmania amazonensis infection in vitro. Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the Leishmania parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-α and MIP-1α levels increased significantly, while the IL-17 A level decreased significantly after treatment. Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.

中文翻译：

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AgNP-PVP-葡甲胺锑酸盐纳米复合材料减少巨噬细胞中的亚马逊利什曼原虫感染

利什曼病是由利什曼原虫属寄生虫引起的一种传染病，具有不同的临床表现。与这种疾病相关的不良反应、免疫抑制和耐药菌株需要开发新药。纳米粒子已显示出作为替代抗利什曼病药物的潜力。我们在之前的一项研究中展示了促进利什曼原虫活性的纳米复合材料的生物合成、表征和理想浓度。在本研究中，我们进行了一项具体分析，以显示 AgNP-PVP-MA（银纳米颗粒-聚乙烯吡咯烷酮-[葡甲胺锑酸盐 (Glucantime®)]）纳米复合材料在体外利什曼原虫感染期间的作用机制。通过超微结构分析，我们观察到显着的改变，例如鞭毛袋和细胞外膜中存在小囊泡，高尔基复合体和线粒体中形成髓鞘样结构，鞭毛和质膜破裂，以及两种进化形式的寄生虫细胞核边缘的电致物质沉积. 此外，治疗后巨噬细胞中的利什曼原虫寄生虫感染指数显着下降，并确定了一氧化氮和活性氧的产生水平。此外，还评估了炎症和促炎细胞因子和趋化因子的产生水平。治疗后IL-4、TNF-α和MIP-1α水平显着升高，而IL-17A水平显着降低。因此，我们在这项研究中证明了 AgNP-PVP-MA 纳米复合材料具有利什曼原虫的潜力，