School of Physics, Technological University Dublin, Kevin Street, Dublin 8, Ireland; Nanolab Research Centre, FOCAS Research Institute, Technological University Dublin, Kevin Street, Dublin 8, Ireland.
School of Physics, Technological University Dublin, Kevin Street, Dublin 8, Ireland; Nanolab Research Centre, FOCAS Research Institute, Technological University Dublin, Kevin Street, Dublin 8, Ireland.
Toxicol In Vitro. 2019 Dec;61:104641. doi: 10.1016/j.tiv.2019.104641. Epub 2019 Sep 4.
Silver nanoparticles (AgNP) are widely used in a variety of consumable products as antibacterial to prevent or treat infection. Unfortunately, evidence exits that AgNP induces inflammation which can worsen with repeated human exposure. However, there is little or no research on how to mitigate these adverse effects due to AgNP induced-toxicity. Here, we investigated if surface modification of AgNP by liposomal encapsulation suppresses AgNP-mediated inflammatory responses in THP1 monocytes and THP1 differentiated macrophages (TDM). AgNP was encapsulated in a dipalmitoyl phosphatidyl choline- (DPPC)/cholesterol-based liposome by extrusion through a 100-nm polycarbonate membrane to form Lipo-AgNP. It was found as expected that AgNP induced significant release of IL-1β, IL-6, IL-8 and TNF-α in THP1 monocytes more than the basal level. Interestingly, release of these cytokines was suppressed by Lipo-AgNP. In TDMs, AgNP and Lipo-AgNP induced IL-8 release (p < .0001), but Lipo-AgNP maintained IL-8 release at levels significantly lower than that of AgNP (p < .01). However, both AgNP and Lipo-AgNP suppressed IL-1β and TNF-α release in LPS-stimulated THP1 monocytes and LPS-stimulated or unstimulated TDM respectively. We finally showed that Lipo-AgNP inhibits STAT-3 and this may be responsible for regulating the uncontrolled inflammation induced by AgNP likely mediated STAT-3 protein expression in LPS stimulated THP1 monocytes and TDMs, both LPS-stimulated and unstimulated. This data showed that Lipo-AgNP suppressed AgNP induced inflammation, making Lipo-AgNP particularly useful in treatment of bacteria induced inflammatory diseases and inflammatory cancers.
银纳米粒子（AgNP）被广泛应用于各种消费品中，作为抗菌剂来预防或治疗感染。不幸的是，有证据表明 AgNP 会引起炎症，而这种炎症在人类反复暴露于 AgNP 时可能会恶化。然而，由于 AgNP 诱导的毒性，如何减轻这些不良反应的研究很少或没有。在这里，我们研究了通过脂质体包封对 AgNP 进行表面修饰是否能抑制 THP1 单核细胞和 THP1 分化的巨噬细胞（TDM）中 AgNP 介导的炎症反应。AgNP 通过在 100nm 聚碳酸酯膜上挤压被包封在二棕榈酰磷脂酰胆碱（DPPC）/胆固醇脂质体中，形成 Lipo-AgNP。正如预期的那样，AgNP 在 THP1 单核细胞中诱导了显著高于基础水平的 IL-1β、IL-6、IL-8 和 TNF-α 的释放。有趣的是，Lipo-AgNP 抑制了这些细胞因子的释放。在 TDMs 中，AgNP 和 Lipo-AgNP 诱导了 IL-8 的释放（p<0.0001），但 Lipo-AgNP 将 IL-8 的释放维持在明显低于 AgNP 的水平（p<0.01）。然而，AgNP 和 Lipo-AgNP 均抑制了 LPS 刺激的 THP1 单核细胞和 LPS 刺激或未刺激的 TDM 中 IL-1β 和 TNF-α 的释放。我们最后表明，Lipo-AgNP 抑制了 STAT-3，这可能是负责调节由 AgNP 诱导的失控性炎症的原因，可能通过 LPS 刺激的 THP1 单核细胞和 TDMs 中 STAT-3 蛋白表达来介导，无论是 LPS 刺激的还是未刺激的。这些数据表明，Lipo-AgNP 抑制了 AgNP 诱导的炎症，使得 Lipo-AgNP 在治疗细菌诱导的炎症性疾病和炎症性癌症方面特别有用。
