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首页> 外文期刊>Archives of Toxicology >PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity toward human lung cells
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PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity toward human lung cells

机译:ORMOSIL纳米颗粒的PEG化可不同程度地调节体外对人肺细胞的毒性

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摘要

ORganically MOdified SILica (ORMOSIL) nanoparticles (NPs) appear promising carriers for the delivery of drugs to target tissues but concerns on possible cytotoxic effects exist. Here, we studied the in vitro responses to ORMOSIL NPs in different types of human lung cells to determine the effects of polyethylene glycol (PEG) coating on NP cytotoxicity. Non-PEG NPs caused a concentration-dependent decrease of viability of all types of cells, while PEG NPs induced deleterious effects and death in carcinoma alveolar type II A549 cells but not in CCD-34Lu fibroblasts and NCI-H2347 adenocarcinoma cells. Reactive oxygen species were detected in cells incubated with PEG NPs, but their deactivation by superoxide dismutase and catalase did not protect A549 cells from death, suggesting that the oxidative stress was not the main determinant of cytotoxicity. Only in A549 cells PEG NPs modulated the transcription of genes involved in inflammation, signal transduction and cell death. Transmission electron microscopy evidenced a unique intracellular localization of PEG NPs in the lamellar bodies of A549 cells, which could be the most relevant factor leading to cytotoxicity by reducing the production of surfactant proteins and by interfering with the pulmonary surfactant system.
机译:有机改性二氧化硅(ORMOSIL)纳米颗粒(NPs)似乎是有前途的载体,可以将药物输送到目标组织,但存在对细胞毒性作用的担忧。在这里,我们研究了在不同类型的人肺细胞中对ORMOSIL NP的体外反应,以确定聚乙二醇(PEG)涂层对NP细胞毒性的影响。非PEG NPs引起所有类型细胞活力的浓度依赖性降低,而PEG NPs在II型癌肺泡A549细胞中诱导有害作用和死亡,而在CCD-34Lu成纤维细胞和NCI-H2347腺癌细胞中则没有。在与PEG NPs一起孵育的细胞中检测到了活性氧,但是它们被超氧化物歧化酶和过氧化氢酶灭活并不能保护A549细胞免于死亡,这表明氧化应激不是细胞毒性的主要决定因素。仅在A549细胞中,PEG NPs调节与炎症,信号转导和细胞死亡有关的基因的转录。透射电镜证实PEG NPs在A549细胞的层状体内具有独特的胞内定位,这可能是通过减少表面活性​​剂蛋白的产生并干扰肺表面活性剂系统而导致细胞毒性的最相关因素。

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