Despite considerable efforts, the properties that drive the cytotoxicity of engineered nanomaterials (ENMs) remain poorly understood. Here, the authors inverstigate a panel of 31 ENMs with different core chemistries and a variety of surface modifications using conventional in vitro assays coupled with omics‐based approaches. Cytotoxicity screening and multiplex‐based cytokine profiling reveals a good concordance between primary human monocyte‐derived macrophages and the human monocyte‐like cell line THP‐1. Proteomics analysis following a low‐dose exposure of cells suggests a nonspecific stress response to ENMs, while microarray‐based profiling reveals significant changes in gene expression as a function of both surface modification and core chemistry. Pathway analysis highlights that the ENMs with cationic surfaces that are shown to elicit cytotoxicity downregulated DNA replication and cell cycle responses, while inflammatory responses are upregulated. These findings are validated using cell‐based assays. Notably, certain small, PEGylated ENMs are found to be noncytotoxic yet they induce transcriptional responses reminiscent of viruses. In sum, using a multiparametric approach, it is shown that surface chemistry is a key determinant of cellular responses to ENMs. The data also reveal that cytotoxicity, determined by conventional in vitro assays, does not necessarily correlate with transcriptional effects of ENMs.

中文翻译：

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工程纳米材料的多参数分析：揭示表面涂层效应

尽管付出了巨大的努力，但人们对工程纳米材料 (ENM) 细胞毒性的特性仍然知之甚少。在这里，作者使用传统的体外测定结合基于组学的方法，对一组具有不同核心化学成分和各种表面修饰的 31 个 ENM 进行了研究。细胞毒性筛选和多重细胞因子分析揭示了原代人单核细胞来源的巨噬细胞和人单核细胞样细胞系 THP-1 之间的良好一致性。细胞低剂量暴露后的蛋白质组学分析表明对 ENM 的非特异性应激反应，而基于微阵列的分析揭示了基因表达作为表面修饰和核心化学的函数的显着变化。通路分析强调，具有阳离子表面的 ENM 可以引发细胞毒性，从而下调 DNA 复制和细胞周期反应，同时上调炎症反应。这些发现通过基于细胞的检测得到验证。值得注意的是，某些小的聚乙二醇化 ENM 被发现没有细胞毒性，但它们会诱导类似于病毒的转录反应。总之，使用多参数方法表明表面化学是细胞对 ENM 反应的关键决定因素。数据还表明，通过传统体外测定确定的细胞毒性并不一定与 ENM 的转录效应相关。