Graphene oxide (GO) and silver nanoparticles (AgNPs) can be formed into a hybrid nanomaterial, known as GOAg nanocomposite, which presents high antibacterial activity. The successful translation of this nanomaterial into medical use depends on critical information about its toxicological profile. In keeping with a Safe-by-design approach, we evaluated the immunotoxicity of GOAg using J774 and primary murine macrophages. The interaction between GOAg and macrophages was investigated with a scanning electron microscope (SEM). High-throughput technologies were employed to evaluate cell viability, apoptosis/necrosis, mitochondrial depolarization and lipid peroxidation. The inflammogenicity of nanomaterials was predicted after quantification of the cytokines IL-1β, TNF-α and IL-10 before and after stimulation with interferon-γ (IFN-γ). The ratio between CD80 and CD206 macrophage populations were also estimated. In addition, the production of nitric oxide (NO) was investigated. SEM surveys revealed the potential of GOAg to induce frustrated phagocytosis. GOAg induced a dose-dependent mitochondrial depolarization, apoptosis and lipid peroxidation to J774 macrophages. GOAg toxicity was not modified in an inflammatory microenvironment, but its toxicity was within the range of concentrations used in bacterial inactivation. GOAg did not induce primary macrophages to significantly produce inflammatory cytokines, and previous macrophage stimulation did not enhance GOAg inflammogenicity. Additionally, the pristine nanomaterials and GOAg do not shift macrophages polarization towards M1. Sublethal concentrations of GOAg did not impair macrophages NO production. Finally, we suggest options for improvement of GOAg nanocomposite in ways that may help minimize its possible adverse outcomes to human health.

中文翻译：

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基于氧化石墨烯和银纳米颗粒的有效杀菌纳米复合材料的体外免疫毒性评估。

氧化石墨烯（GO）和银纳米颗粒（AgNPs）可以形成一种混合纳米材料，称为GOAg纳米复合材料，具有很高的抗菌活性。这种纳米材料能否成功转化为医疗用途，取决于其毒理学特征的关键信息。与“按设计设计”的方法保持一致，我们使用J774和原代鼠巨噬细胞评估了GOAg的免疫毒性。GOAg和巨噬细胞之间的相互作用用扫描电子显微镜（SEM）进行了研究。高通量技术用于评估细胞活力，细胞凋亡/坏死，线粒体去极化和脂质过氧化。在对干扰素-γ（IFN-γ）刺激之前和之后的细胞因子IL-1β，TNF-α和IL-10进行定量分析后，可以预测纳米材料的发炎性。还估计了CD80和CD206巨噬细胞种群之间的比率。另外，研究了一氧化氮（NO）的产生。SEM调查显示，GOAg可能导致沮丧的吞噬作用。GOAg诱导剂量依赖性的J774巨噬细胞线粒体去极化，凋亡和脂质过氧化。GOAg毒性在炎性微环境中没有改变，但其毒性在细菌灭活所用的浓度范围内。GOAg不会诱导原代巨噬细胞显着产生炎性细胞因子，以前的巨噬细胞刺激也不会增强GOAg的致炎性。此外，原始的纳米材料和GOAg不会使巨噬细胞极化移向M1。亚致死浓度的GOAg不会损害巨噬细胞的NO产生。最后，