Nanoparticles (NPs) are important in a variety of sectors, including disease diagnostics, medicine, nutrition, and many other industries. The risk of human exposure demands an early evaluation of both the basic dynamics of NPs’ interaction with biological systems and their potential consequences. Deciphering these occurrences will provide critical information regarding the health hazards and safety advantages associated with next-generation nanoformulations in clinical practice. We examined the HepG2 cell line in a systematic manner to determine the cellular response to single-walled carbon nanotubes (SWCNTs) and zinc oxide (ZnO) NPs. With the use of high-throughput transcriptomic methods, we found that both NPs induce comparable dysregulation of the endocytic and proteasomal complex genes in liver hepatocellular carcinoma cells, at levels (> 80 percent cell viability) that do not cause over-toxicity at early incubation period (6 h). SWCNT and ZnO NPs were shown to enter cells through clathrin-mediated pathways, affecting cytoskeleton gene expression, DNA damage and repair, protein ubiquitination, and cell transcriptional machinery. Our findings indicate that early response strategies activate stress-related mechanisms. Finally, this method for studying nanomaterial–cell interactions demonstrates how changes in the transcriptome profile may predict downstream consequences even at doses that do not cause acute toxicity.

中文翻译：

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RNA测序揭示的非细胞毒性剂量下，ZnO纳米颗粒和SWCNT诱导HepG2细胞的一般应激反应途径

纳米粒子 (NP) 在各个领域都很重要，包括疾病诊断、医学、营养和许多其他行业。人类暴露的风险要求对 NPs 与生物系统相互作用的基本动态及其潜在后果进行早期评估。破译这些事件将提供有关与临床实践中下一代纳米制剂相关的健康危害和安全优势的关键信息。我们以系统的方式检查了 HepG2 细胞系，以确定细胞对单壁碳纳米管 (SWCNT) 和氧化锌 (ZnO) NPs 的反应。通过使用高通量转录组学方法，我们发现两种 NPs 在肝细胞癌细胞中诱导内吞和蛋白酶体复合物基因的相当的失调，在水平（> 80% 的细胞活力）在早期潜伏期（6 小时）不会引起过度毒性。SWCNT 和 ZnO NPs 通过网格蛋白介导的途径进入细胞，影响细胞骨架基因表达、DNA 损伤和修复、蛋白质泛素化和细胞转录机制。我们的研究结果表明，早期反应策略激活了与压力相关的机制。最后，这种研究纳米材料-细胞相互作用的方法证明了转录组谱的变化如何预测下游后果，即使在不引起急性毒性的剂量下也是如此。和细胞转录机制。我们的研究结果表明，早期反应策略激活了与压力相关的机制。最后，这种研究纳米材料-细胞相互作用的方法证明了转录组谱的变化如何预测下游后果，即使在不引起急性毒性的剂量下也是如此。和细胞转录机制。我们的研究结果表明，早期反应策略激活了与压力相关的机制。最后，这种研究纳米材料-细胞相互作用的方法证明了转录组谱的变化如何预测下游后果，即使在不引起急性毒性的剂量下也是如此。