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金属氧化物纳米颗粒通过诱导坏死细胞死亡表现出抗棘阿米巴原虫的特性。

Metal Oxide Nanoparticles Exhibit Anti-Acanthamoeba castellanii Properties by Inducing Necrotic Cell Death.

机构信息

Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500, Subang Jaya, Selangor, Malaysia.

Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University Edinburgh, Edinburgh, EH14 4AS, UK.

出版信息

Acta Parasitol. 2024 Sep;69(3):1717-1723. doi: 10.1007/s11686-024-00891-2. Epub 2024 Aug 17.

DOI:10.1007/s11686-024-00891-2
PMID:39153011
Abstract

PURPOSE

The treatment of amoebic infections is often problematic, largely due to delayed diagnosis, amoebae transformation into resistant cyst form, and lack of availability of effective chemotherapeutic agents. Herein, we determined anti-Acanthamoeba castellanii properties of three metal oxide nanoparticles (TiO, ZrO, and AlO).

METHODS

Amoebicidal assays were performed to determine whether metal oxide nanoparticles inhibit amoebae viability. Encystation assays were performed to test whether metal oxide nanoparticles inhibit cyst formation. By measuring lactate dehydrogenase release, cytotoxicity assays were performed to determine human cell damage. Hoechst 33342/PI staining was performed to determine programmed cell death (apoptosis) and necrosis in A. castellanii.

RESULTS

TiO-NPs significantly inhibited amoebae viability as observed through amoebicidal assays, as well as inhibited their phenotypic transformation as evident using encystation assays, and showed limited human cell damage as observed by measuring lactate dehydrogenase assays. Furthermore, TiO-NPs altered parasite membranes and resulted in necrotic cell death as determined using double staining cell death assays with Hoechst33342/Propidium iodide (PI) observed through chromatin condensation. These findings suggest that TiO-NPs offers a potential viable avenue in the rationale development of therapeutic interventions against Acanthamoeba infections.

摘要

目的

阿米巴感染的治疗常常存在问题,这主要是由于诊断延迟、阿米巴转化为耐药囊形式以及缺乏有效的化学治疗药物。在此,我们研究了三种金属氧化物纳米粒子(TiO、ZrO 和 AlO)对耐格里原虫的抗阿米巴特性。

方法

采用杀阿米巴试验来确定金属氧化物纳米粒子是否抑制阿米巴的活力。采用囊形成试验来检测金属氧化物纳米粒子是否抑制囊形成。通过测量乳酸脱氢酶的释放,进行细胞毒性试验来确定人类细胞的损伤。采用 Hoechst 33342/PI 染色来确定耐格里原虫中的程序性细胞死亡(凋亡)和坏死。

结果

TiO-NPs 通过杀阿米巴试验显著抑制了阿米巴的活力,通过囊形成试验抑制了其表型转化,并通过测量乳酸脱氢酶试验显示对人类细胞的损伤有限。此外,TiO-NPs 改变了寄生虫的膜,并导致了坏死性细胞死亡,这通过使用 Hoechst33342/碘化丙啶(PI)双重染色细胞死亡试验来确定,通过染色质凝聚观察到。这些发现表明,TiO-NPs 为针对耐格里原虫感染的治疗干预措施的合理发展提供了一种有前途的可行途径。

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