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纳米氧化铈在神经系统应用中的安全使用的体外和体内生物相容性评估。

In vitro and in vivo assessment of nanoceria biocompatibility for their safe use in nervous system applications.

作者信息

Fernández-Bertólez Natalia, Martínez Luisa, Ramos-Pan Lucía, Touzani Assia, Costa Carla, Laffon Blanca, Valdiglesias Vanessa

机构信息

Universidade da Coruña, Grupo NanoToxGen, Centro Interdisciplinar de Química e Bioloxía - CICA, Departamento de Biología, Facultad de Ciencias, Campus A Zapateira s/n, A Coruña 15071, Spain; Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, As Xubias, A Coruña 15006, Spain.

Universidade da Coruña, Grupo NanoToxGen, Centro Interdisciplinar de Química e Bioloxía - CICA, Departamento de Biología, Facultad de Ciencias, Campus A Zapateira s/n, A Coruña 15071, Spain.

出版信息

J Hazard Mater. 2025 Mar 15;486:137041. doi: 10.1016/j.jhazmat.2024.137041. Epub 2024 Dec 31.

Abstract

Nanoceria, or cerium dioxide nanoparticles (CeO NP), are increasingly employed in a number of industrial and commercial applications. Hence, the environmental presence of these nanoparticles is growing progressively, enhancing the global concern on their potential health effects. Recent studies suggest that nanoceria may also have promising biomedical applications particularly in neurodegenerative and brain-related pathologies, but studies addressing their toxicity, and specifically on the nervous system, are still scarce, and their potential adverse effects and action mechanism are not totally understood yet. The objective of this work was to assess the biological behaviour of CeO NP in vitro in human nervous systems cells, and in vivo in Drosophila melanogaster to characterize their safety for exposed individuals and verify their suitability to be further employed in diagnosis and treatment of nervous system disorders. Cell cycle alterations, late apoptosis rate and DNA damage (comet and γH2AX assays), were determined in neuronal SH-SY5Y and glial A172 cells treated with nanoceria. Moreover, the survival rate, morphological changes and behavioural alterations were analysed in D. melanogaster individuals chronically exposed to CeO NP. The results obtained from the in vitro assessment showed that the nanoceria generally presented a good biocompatibility with scarce cyto- or genotoxic effects, essentially depending the exposure time and cell type, and being restricted to the longer exposure periods. Nevertheless, decrease in adult size and alterations observed in the larval crawling in the in vivo assays highlight the need of further investigations before establishing clinical uses of nanoceria.

摘要

纳米氧化铈,即二氧化铈纳米颗粒(CeO NP),越来越多地应用于许多工业和商业领域。因此,这些纳米颗粒在环境中的存在日益增加,这也加剧了全球对其潜在健康影响的担忧。最近的研究表明,纳米氧化铈在生物医学应用方面也具有广阔前景,尤其是在神经退行性疾病和脑部相关病症中,但针对其毒性,特别是对神经系统毒性的研究仍然很少,其潜在的不良反应和作用机制尚未完全明确。本研究的目的是评估CeO NP在体外人神经系统细胞中的生物学行为,以及在体内果蝇中的生物学行为,以表征其对暴露个体的安全性,并验证其在神经系统疾病诊断和治疗中进一步应用的适用性。在用纳米氧化铈处理的神经元SH-SY5Y细胞和胶质A172细胞中,测定细胞周期变化、晚期凋亡率和DNA损伤(彗星试验和γH2AX试验)。此外,还分析了长期暴露于CeO NP的果蝇个体的存活率、形态变化和行为改变。体外评估结果表明,纳米氧化铈通常具有良好的生物相容性,细胞毒性或遗传毒性作用较小,这主要取决于暴露时间和细胞类型,且仅限于较长的暴露时间。然而,体内试验中观察到的成虫体型减小和幼虫爬行行为改变表明,在确定纳米氧化铈的临床用途之前,还需要进一步研究。

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