Mesoporous nanoparticles are an interesting drug delivery system that has generated considerable attention in the biomedical sector. Despite recent attempts to conduct safety assessments using traditional methods based on phenotypic data, our understanding of the underlying molecular processes produced by mesoporous NPs is still in its infancy. In the present study, RNA sequencing was used to assess the biological perturbations and the pathways induced in response to early exposure of two different mesoporous NPs; mesoporous silica NPs and mesoporous carbon NPs in human liver hepatocellular carcinoma cells. In order to better understand the risks associated with NPs, it is required to consider the initial low dose exposure effects that mimic the real exposure scenario. No overt toxicity was detected in the MTT assay when performed at 6 hours at low concentrations (MCN 25 g/ml and MSN 15 g/ml) of NPs; thus, RNA sequencing was used at this concentration. Our transcriptomics analysis showed significant differences in the expression of many genes after exposure to both NPs. Surprisingly, both NPs frequently deregulated 52.9 percent of upregulated and 42 percent of downregulated genes. Gene ontology categories, in particular, revealed comparable perturbations of biological reactions in the cellular system. HepG2 cells reacted to mesoporous NPs by allowing alterations in genes involved in cytoskeleton reorganisation (ATAT1, DMTN, PTK2 and PFN2). Exposure to mesoporous NPs increased transcripts expressing ubiquitin ligase (RNF187, ARIH2, VHL, and RAB40C), transferase (FBXO3 and WDSUB1), conjugating (UBE2J2), and also proteasomal subunits (PSMD2, PSMD13) enzymes, indicating that protein turnover rates are altered in response to environmental damage. In addition, DNA damage and DNA damage checkpoint genes were upregulated, indicating that NPs induced stress in the cells. These finding showed low dosage acute exposure have comparable responses between mesoporous NPs.

中文翻译：

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介孔纳米粒子低剂量暴露后细胞系统的不同转录组学反应

介孔纳米粒子是一种有趣的药物递送系统，在生物医学领域引起了相当大的关注。尽管最近尝试使用基于表型数据的传统方法进行安全性评估，但我们对介孔 NP 产生的潜在分子过程的理解仍处于起步阶段。在本研究中，RNA 测序用于评估两种不同介孔 NP 早期暴露引起的生物扰动和通路；人肝细胞癌细胞中的介孔二氧化硅纳米粒子和介孔碳纳米粒子。为了更好地了解与 NPs 相关的风险，需要考虑模拟真实暴露场景的初始低剂量暴露效应。当在低浓度（MCN 25 g/ml 和 MSN 15 g/ml）的 NPs 下进行 6 小时时，MTT 测定未检测到明显的毒性；因此，在此浓度下使用 RNA 测序。我们的转录组学分析显示，在暴露于两种 NP 后，许多基因的表达存在显着差异。令人惊讶的是，两种 NPs 经常解除 52.9% 的上调基因和 42% 的下调基因。特别是基因本体论类别揭示了细胞系统中生物反应的可比扰动。HepG2 细胞通过改变参与细胞骨架重组的基因（ATAT1、DMTN、PTK2 和 PFN2）对介孔 NP 起反应。暴露于介孔 NP 会增加表达泛素连接酶（RNF187、ARIH2、VHL 和 RAB40C）、转移酶（FBXO3 和 WDSUB1）、结合（UBE2J2）、以及蛋白酶体亚基（PSMD2、PSMD13）酶，表明蛋白质周转率会因环境损害而改变。此外，DNA 损伤和 DNA 损伤检查点基因上调，表明 NPs 在细胞中诱导了应激。这些发现表明，低剂量急性暴露在介孔 NP 之间具有可比的反应。