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在成骨细胞中表达自噬基因时,内吞的银纳米颗粒在溶酶体中降解,形成次级纳米颗粒结构。

Endocytosed silver nanoparticles degrade in lysosomes to form secondary nanoparticle structures during expression of autophagy genes in osteogenic cells.

机构信息

Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.

Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.

出版信息

Nanomedicine. 2021 Apr;33:102355. doi: 10.1016/j.nano.2020.102355. Epub 2021 Jan 15.

DOI:10.1016/j.nano.2020.102355
PMID:33454429
Abstract

Silver nanoparticles (AgNPs) are increasingly used in combination with biomaterials, such as bone grafts, to provide antimicrobial properties. Our research focused on the cytotoxic and intracellular uptake mechanism of AgNPs on osteogenic cells, and the affected gene expression of osteoblasts exposed to AgNPs. Osteoblast cells were found to be relatively resistant to AgNP exposure, compared to osteoclasts, with a higher IC and fewer adverse morphological features. AgNPs were endocytosed within lysosomes, which resulted in the secondary internal formation of curved Ag nano-chains assemblies within the cytosol. Furthermore, osteoblasts demonstrated an oxidative stress response, with autophagic cell death mechanisms, as indicated from qRT-PCR analysis, with sustained upregulation of the protective gene Heme Oxygenase 1 reaching 86-fold by 48 hours (10 μg/mL). The internalization and fate of AgNPs in osteogenic cells, and the resulting impact on gene expression over time provide further understanding of the nanotoxicity mechanism of AgNPs.

摘要

银纳米粒子(AgNPs)越来越多地与生物材料(如骨移植物)结合使用,以提供抗菌性能。我们的研究集中在 AgNPs 对成骨细胞的细胞毒性和细胞内摄取机制,以及暴露于 AgNPs 的成骨细胞受影响的基因表达上。与破骨细胞相比,成骨细胞对 AgNP 暴露的抵抗力相对较强,IC 较高,不良形态特征较少。AgNPs 被内吞到溶酶体中,导致溶酶体中原位形成弯曲的 Ag 纳米链组装体。此外,成骨细胞表现出氧化应激反应,自噬细胞死亡机制,如 qRT-PCR 分析所示,保护性基因血红素加氧酶 1 的持续上调在 48 小时(10μg/ml)时达到 86 倍。AgNPs 在成骨细胞中的内化和命运,以及对基因表达随时间的影响,为 AgNPs 的纳米毒性机制提供了进一步的理解。

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