Cell uptake and oral absorption of titanium dioxide nanoparticles

Cell uptake and oral absorption of titanium dioxide nanoparticles
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DOI:
10.1016/j.toxlet.2014.04.014
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发表时间:
2014-07-15
期刊:
影响因子:
3.5
通讯作者:
Vazquez-Campos, S.
Vazquez-Campos, S.
中科院分区:
医学3区
文献类型:
--
作者:
Janer, G.;Mas del Molino, E.;Vazquez-Campos, S.

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大量的努力投入到体外测试的发展,以评估纳米材料(NM)的毒性。为了评估在体外毒性试验中确定的不良反应的相关性,对NM的生物学特性的透彻理解至关重要。我们使用不同的体外和体内测试方法来评估二氧化钛纳米颗粒(TiO 2 NPs)的细胞摄取和口服吸收。这些NP在体外容易被A549细胞(致癌的人肺泡基底上皮细胞)摄取。这种快速吸收与分化的Caco-2单层系统(人上皮结直肠腺癌细胞)和大鼠经口灌胃给药后的极低口服吸收形成对比。在该口服研究中,通过ICP-MS在评价的任何组织(包括小肠、派尔集合淋巴结、肠系膜淋巴结、肝脏和脾脏)中均未记录到钛水平显著增加。在小肠切片中通过TEM未观察到NP,除了来自派尔集合淋巴结区域的细胞的细胞质中的几个颗粒。Peyer集合淋巴结中NP的观察结果表明,Caco-2单层系统可能低估了NP的口服吸收潜力,并且可以通过在共培养中包括M细胞来改善该模型。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Large efforts are invested on the development of in vitro tests to evaluate nanomaterial (NM) toxicity. In order to assess the relevance of the adverse effects identified in in vitro toxicity tests a thorough understanding of the biokinetics of NMs is critical. We used different in vitro and in vivo test methods to evaluate cell uptake and oral absorption of titanium dioxide nanoparticles (TiO2 NPs). These NPs were readily uptaken by A549 cells (carcinomic human alveolar basal epithelial cells) in vitro. Such rapid uptake contrasted with a very low oral absorption in a differentiated Caco-2 monolayer system (human epithelial colorectal adenocarcinoma cells) and after oral gavage administration to rats. In this oral study, no significant increase in the levels of titanium was recorded by ICP-MS in any of the tissues evaluated (including among other: small intestine, Peyer's patches, mesenteric lymph nodes, liver, and spleen). No NPs were observed by TEM in sections of the small intestine, except for several particles in the cytoplasm of a cell from a Peyer's Patch area. The observation of NPs in Peyer's Patch suggests that the Caco-2 monolayer system is likely to underestimate the potential for oral absorption of NPs and that the model could be improved by including M-cells in co-culture. (C) 2014 Elsevier Ireland Ltd. All rights reserved.