Toxicity and mechanism of mesoporous silica nanoparticles in eyes
Toxicity and mechanism of mesoporous silica nanoparticles in eyes
复制标题
介孔二氧化硅纳米粒子对眼的毒性及机制
DOI：
10.1039/d0nr03208e
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发表时间：
2020-07-07
期刊：
影响因子：
6.7
通讯作者：
Xu, Haiwei
中科院分区：
文献类型：
--
作者：
Chen, Xia;Zhu, Shuang;Xu, Haiwei
纳米材料对眼睛的安全性研究仍处于早期阶段。在这项研究中，我们将重点放在纳米颗粒的一个重要特征（大表面积）对评估眼睛安全性的影响上。为此，首次采用介孔二氧化硅纳米粒子（MSiNP）作为模型来评估其对眼睛的毒性。 MSiNP 的孔隙率赋予它们较大的表面积以及附着到周围化学或生物分子的能力，进一步增强其表面反应性和毒性作用。因此，为了更好地模拟真实环境中的 MSiNP 暴露，我们还在系统中引入了其他有害物质，例如银离子 (Ag+)，然后研究了它们的协同纳米毒性。我们的结果表明，细胞活力、细胞凋亡、活性氧 (ROS) 产生和 DNA 损伤实验证明，暴露于 MSiNPs-Ag(+) 甚至安全剂量的 Ag(+) 会比单独使用 MSiNPs 产生更显着的毒性。 RNA 测序分析表明，mRNA 监测信号通路在调节 MSiNPs-Ag+ 诱导的细胞毒性中发挥着独特的作用。除此之外，与 MSiNPs 相比，暴露于 MSiNPs-Ag(+) 的大鼠模型中观察到严重的角膜损伤和干眼症。最重要的是，我们还提出了一种基于蛋白电晕的疗法来治疗 MSiNP 引起的角膜疾病，其中角膜损伤可以通过胎牛血清 (FBS) 治疗来挽救。
The study on the safety of nanomaterials in eyes is still in its early stages. In this study, we put our focus on the effect of one important nanoparticle feature - large surface area - to assess eye safety. To this end, mesoporous silica nanoparticles (MSiNPs) were for the first time employed as a model to evaluate their toxicity in eyes. The porosity of the MSiNPs endows them with a large surface area and the ability to attach to surrounding chemical or biological molecules, further enhancing their surface reactivity and toxic effects. Therefore, to better mimic MSiNP exposure in real environments, we also introduced other hazardous substances such as silver ions (Ag+) to the system and then investigated their synergistic nanotoxicity. Our results showed that the exposure to MSiNPs-Ag(+)and even Ag(+)at a safe dose, resulted in more significant toxicity than the MSiNPs alone, as evidenced from cell viability, apoptosis, reactive oxygen species (ROS) production, and DNA damage experiments. RNA-Sequencing analysis revealed that the mRNA surveillance signalling pathway plays a unique role in regulating MSiNPs-Ag+-induced cytotoxicity. Besides this, severe corneal damage and dry eye were observed in rat models upon exposure to MSiNPs-Ag(+)compared to MSiNPs. Most importantly, we also proposed a protein corona-based therapy to treat MSiNP-induced corneal disease, where the corneal damage could be rescued by fetal bovine serum (FBS) treatment.