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胶态铜纳米粒子诱导 RAW 264.7 巨噬细胞系氧化应激细胞毒性。

Oxidative Stress Induced Cytotoxicity of Colloidal Copper Nanoparticles on RAW 264.7 Macrophage Cell Line.

机构信息

Department Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, India.

School of Physics and Materials Science, Thapar Institute of Engineering and Technology, Patiala 147004, India.

出版信息

J Nanosci Nanotechnol. 2021 Oct 1;21(10):5066-5074. doi: 10.1166/jnn.2021.19365.

DOI:10.1166/jnn.2021.19365
PMID:33875092
Abstract

Copper is an essential trace mineral that plays an important role in various physiological processes of human body and also possesses excellent antimicrobial properties, however its high dose results in the formation of free-radicals, which can induce cytotoxicity through chromosomal and DNA damage. Therefore, cytotoxicity of colloidal copper nanoparticles (CuNPs) on murine macrophage cell line (RAW 264.7) was studied to understand the correlation between the cytotoxicity and the nanoparticle yield. Three identical sets of CuNPs with similar physical properties having hydrodynamic particle size of 11-14 nm were prepared by chemical reduction method with target yield of 0.2 g, 0.3 g and 0.4 g. CuNPs exhibited dose-dependent (0.001-100 μg/mL) cytotoxicity due to the mitochondrial damage as indicated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. Oxidative stress induced by reactive oxygen species (ROS) in RAW 246.7 macrophage cell lines exposed to CuNPs was the primary cause of observed cytotoxicity in all CuNPs test samples. Morphological changes in cells also indicated strong dose-dependent oxidative damage by CuNPs. IC (half maximal inhibitory concentration) values of CuNPs were independent of nanoparticle yield. This suggests that per batch variation in CuNPs yield from 0.2 g to 0.4 g had no negative correlation with their toxicity that makes CuNPs a potential candidate for further development of nanotherapeutics and anticancer drugs.

摘要

铜是一种必需的微量元素,在人体的各种生理过程中发挥着重要作用,同时也具有优异的抗菌性能。然而,高剂量的铜会形成自由基,通过染色体和 DNA 损伤引发细胞毒性。因此,研究了胶体铜纳米粒子(CuNPs)对小鼠巨噬细胞系(RAW 264.7)的细胞毒性,以了解细胞毒性与纳米粒子产率之间的相关性。通过化学还原法制备了三组具有相似物理性质的、水动力粒径为 11-14nm 的相同 CuNPs,目标产率分别为 0.2g、0.3g 和 0.4g。CuNPs 表现出剂量依赖性(0.001-100μg/mL)的细胞毒性,这是由于 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)测定法所示的线粒体损伤。暴露于 CuNPs 的 RAW 246.7 巨噬细胞系中活性氧(ROS)诱导的氧化应激是所有 CuNPs 测试样品中观察到细胞毒性的主要原因。细胞形态的变化也表明 CuNPs 具有强烈的剂量依赖性氧化损伤。CuNPs 的 IC(半最大抑制浓度)值与纳米粒子产率无关。这表明,CuNPs 批产量从 0.2g 到 0.4g 的变化与它们的毒性没有负相关,这使得 CuNPs 成为进一步开发纳米治疗和抗癌药物的潜在候选者。

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