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生物源银纳米粒子(AgNp-Bio)可降低 HeLa 细胞中的弓形虫感染和增殖,并通过类似细胞凋亡的机制诱导速殖子自噬和死亡。

Biogenic silver nanoparticles (AgNp-Bio) reduce Toxoplasma gondii infection and proliferation in HeLa cells, and induce autophagy and death of tachyzoites by apoptosis-like mechanism.

机构信息

Laboratory of Immunoparasitology of Neglected Diseases and Cancer - LIDNC, State University of Londrina, PR, Brazil.

Carlos Chagas Institute (ICC/FIOCRUZ/PR), Curitiba, PR, Brazil.

出版信息

Acta Trop. 2021 Oct;222:106070. doi: 10.1016/j.actatropica.2021.106070. Epub 2021 Jul 28.

Abstract

Toxoplasma gondii is a protozoan parasite that can cause severe and debilitating diseases, especially in immunocompromised individuals. The available treatment is based on drugs that have low efficacy, high toxicity, several adverse effects, and need long periods of treatment. Thus, the search for therapeutic alternatives is urgently needed. Biogenic silver nanoparticles (AgNp-Bio) have been associated with several biological effects, as antiproliferative, pro-apoptotic, antioxidant, antiviral, antifungal, and antiprotozoal activity. Thus, the objective was evaluating AgNp-Bio effect on HeLa cells infected with T. gondii (RH strain). First, nontoxic AgNp-Bio concentrations for HeLa cells (1.5 - 6 µM) were determined, which were tested on cells infected with T. gondii. A significant reduction in infection, proliferation, and intracellular parasitic load was observed, also an increase in ROS and IL-6. Additionally, the evaluation of the action mechanisms of the parasite showed that AgNp-Bio acts directly on tachyzoites, inducing depolarization of the mitochondrial membrane, ROS increase, and lipid bodies accumulation, as well as triggering an autophagic process, causing damage to the parasite membrane, and phosphatidylserine exposure. Based on this, it was inferred that AgNp-Bio affects T. gondii by inducing immunomodulation and microbicidal molecules produced by infected cells, and acts on parasites, by inducing autophagy and apoptosis.

摘要

刚地弓形虫是一种原生动物寄生虫,可导致严重和虚弱的疾病,特别是在免疫功能低下的个体中。现有的治疗方法基于疗效低、毒性高、多种不良反应和需要长期治疗的药物。因此,迫切需要寻找治疗替代方法。生物源银纳米粒子(AgNp-Bio)与多种生物学效应相关,如抗增殖、促凋亡、抗氧化、抗病毒、抗真菌和抗原生动物活性。因此,本研究的目的是评估 AgNp-Bio 对感染刚地弓形虫(RH 株)的 HeLa 细胞的影响。首先,确定了对 HeLa 细胞(1.5-6µM)无毒的 AgNp-Bio 浓度,并用其对感染刚地弓形虫的细胞进行测试。观察到感染、增殖和细胞内寄生虫负荷显著减少,ROS 和 IL-6 增加。此外,对寄生虫作用机制的评估表明,AgNp-Bio 直接作用于速殖子,诱导线粒体膜去极化、ROS 增加和脂滴积累,以及触发自噬过程,导致寄生虫膜损伤和磷脂酰丝氨酸暴露。基于此,可以推断出 AgNp-Bio 通过诱导感染细胞产生的免疫调节和杀菌分子来影响刚地弓形虫,并通过诱导自噬和细胞凋亡来作用于寄生虫。

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