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Abstract：
With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.
摘要：
随着纳米技术的发展，对纳米粒子(NPs)潜在不利影响的担忧，尤其是呼吸道.不良结果通路（AOP）最近已成为深入研究的主题，以便更好地了解NP毒性的机制。因此有望预测与NP暴露相关的健康风险。在这里，我们提出了一种推定的AOP使用新兴的纳米材料称为碳点（CD）的NPs的肺毒性，以及体内和体外实验方法。我们首先研究了单次施用CD对小鼠气道的影响。我们发现CD诱导急性肺部炎症，并将气道巨噬细胞鉴定为CD的靶细胞。然后，我们在巨噬细胞的体外模型中研究了CD诱导的细胞反应。我们观察到CD被这些细胞内化（分子初始事件）并诱导一系列关键事件，包括溶酶体完整性的丧失和线粒体破坏（细胞器反应），以及氧化应激，炎症体激活，炎性细胞因子上调和巨噬细胞死亡（细胞反应）。所有这些作用都会触发肺部炎症，因为组织反应可能导致急性肺损伤。
