Zhou Gang, Zhang Jin, Pan Chun, Liu Naicheng, Wang Zhenheng, Zhang Junfeng
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No. 163, Xianlin Avenue, Qixia District, Nanjing 210023, China.
School of Medicine, Nanjing University, No. 22, Hankou Road, Gulou District, Nanjing 210093, China.
Molecules. 2017 Jul 27;22(8):1240. doi: 10.3390/molecules22081240.
Fe₃O₄ nanoparticles (Fe₃O₄ NPs) have been used for medical and drug applications, although the mechanisms of cellular uptake and transport need to be further evaluated under inflammatory conditions. In the present study, we investigated the uptake of Fe₃O₄ NPs (20, 50, 100, and 200 nm) by intestinal epithelial cells under inflammatory conditions via the light scattering of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) techniques. The results of the correlation analysis indicated that the uptake ratios of Fe₃O₄ NPs by intestinal epithelial cells under inflammatory conditions were higher than those under the control conditions. The transportation ratios of NPs by inflammatory Caco-2 cells increased almost 0.8-1.2 fold compared to the control. The internalization of the Fe₃O₄ NPs in Caco-2 cells was mediated by clathrin-related routes in both the control and an interleukin-1β (IL-1β)-induced inflammatory condition. The level of mRNA of clathrin expressed in Caco-2 cells that were stimulated by IL-1β was almost three times more than the control. Consistently with the mRNA expression, the level of protein in the clathrin was upregulated. Additionally, it was verified for the first time that the expression of clathrin was upregulated in IL-1β-stimulated Caco-2 cells. Collectively, these results provided a further potential understanding about the mechanism of Fe₃O₄ NPs' uptake by intestinal epithelial cells under inflammatory conditions.
四氧化三铁纳米颗粒（Fe₃O₄ NPs）已被用于医学和药物应用，尽管在炎症条件下细胞摄取和转运的机制仍需进一步评估。在本研究中，我们通过流式细胞术的光散射和电感耦合等离子体质谱（ICP-MS）技术，研究了炎症条件下肠道上皮细胞对Fe₃O₄ NPs（20、50、100和200纳米）的摄取情况。相关性分析结果表明，炎症条件下肠道上皮细胞对Fe₃O₄ NPs的摄取率高于对照条件下的摄取率。与对照相比，炎症性Caco-2细胞对纳米颗粒的转运率增加了近0.8至1.2倍。在对照和白细胞介素-1β（IL-1β）诱导的炎症条件下，Caco-2细胞中Fe₃O₄ NPs的内化均由网格蛋白相关途径介导。IL-1β刺激的Caco-2细胞中表达的网格蛋白mRNA水平几乎是对照的三倍。与mRNA表达一致，网格蛋白中的蛋白质水平上调。此外，首次证实IL-1β刺激的Caco-2细胞中网格蛋白的表达上调。总的来说，这些结果为炎症条件下肠道上皮细胞摄取Fe₃O₄ NPs的机制提供了进一步的潜在认识。
