Department of Neurobiology, Institute of Anatomy, University of Aarhus, Building 1233/1234, Wilhelm Meyers Allé, DK-8000 Aarhus C, Denmark.
Part Fibre Toxicol. 2007 Oct 19;4:10. doi: 10.1186/1743-8977-4-10.
The study aims at revealing the fate of nanoparticles administered intravenously and intraperitoneally to adult female mice, some of which were pregnant. Gold nanoparticles were chosen as a model because these particles have been found to be chemically inert and at the same time are easily traced by autometallography (AMG) at both ultrastructural and light microscopic levels.
Gold nanoparticles were injected intravenously (IV) or intraperitoneally (IP) and traced after 1, 4 or 24 hours. For IV injections 2 and 40 nm particles were used; for IP injections 40 nm particles only. The injected nanoparticles were found in macrophages only, and at moderate exposure primarily in the Kupffer cells in the liver. IV injections resulted in a rapid accumulation/clustering of nanoparticles in these liver macrophages, while the uptake in spleen macrophages was moderate. IP injections were followed by a delayed uptake in the liver and included a moderate uptake in macrophages located in mesenteric lymph nodes, spleen and small intestine. Ultrastructurally, the AMG silver enhanced nanocrystals were found in lysosome-like organelles of the Kupffer cells and other macrophages wherever located.Accumulations of gold nanoparticles were not found in any other organs analysed, i.e. kidneys, brain, lungs, adrenals, ovaries, placenta, and fetal liver, and the control animals were all void of AMG staining.
Our results suggest that: (1) inert gold nanoparticles do not penetrate cell membranes by non-endocytotic mechanisms, but are rather taken up by endocytosis; (2) gold nanoparticles, independent of size, are taken up primarily by Kupffer cells in the liver and secondarily by macrophages in other places; (3) gold nanoparticles do not seem to penetrate the placenta barrier; (4) the blood-brain barrier seems to protect the central nervous system from gold nanoparticles; (5) 2 nanometer gold particles seem to be removed not only by endocytosis by macrophages, and we hypothesize that part of these tiny nanoparticles are released into the urine as a result of simple filtration in the renal glomeruli.
本研究旨在揭示静脉内和腹腔内给予成年雌性小鼠（其中一些处于妊娠状态）的纳米颗粒的命运。选择金纳米颗粒作为模型，因为这些颗粒已被发现具有化学惰性，同时在超微结构和光镜水平上很容易通过自动金属染色（AMG）进行追踪。
静脉内（IV）或腹腔内（IP）注射金纳米颗粒，并在 1、4 或 24 小时后进行追踪。对于 IV 注射，使用了 2 和 40nm 颗粒；对于 IP 注射，仅使用 40nm 颗粒。注射的纳米颗粒仅在巨噬细胞中被发现，在中度暴露下主要在肝脏的枯否细胞中。IV 注射导致纳米颗粒在这些肝巨噬细胞中迅速聚集/聚类，而在脾巨噬细胞中的摄取则适度。IP 注射后，肝脏摄取延迟，并包括在肠系膜淋巴结、脾和小肠中定位的巨噬细胞中的适度摄取。超微结构上，在位于何处的枯否细胞和其他巨噬细胞的溶酶体样细胞器中发现了 AMG 银增强纳米晶体。在分析的其他器官中未发现金纳米颗粒的积聚，即肾脏、大脑、肺、肾上腺、卵巢、胎盘和胎肝，对照组动物均无 AMG 染色。
我们的结果表明：（1）惰性金纳米颗粒不会通过非胞吞作用机制穿透细胞膜，而是通过胞吞作用被摄取；（2）金纳米颗粒，无论大小如何，主要被肝脏中的枯否细胞摄取，其次是其他部位的巨噬细胞；（3）金纳米颗粒似乎不会穿透胎盘屏障；（4）血脑屏障似乎保护中枢神经系统免受金纳米颗粒的侵害；（5）2nm 金颗粒似乎不仅被巨噬细胞通过胞吞作用去除，我们假设其中一部分微小的纳米颗粒由于在肾小球中的简单过滤而被释放到尿液中。
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