Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease
Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease
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DOI：
10.1186/1743-8977-10-19
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发表时间：
2013-05-16
影响因子：
10
通讯作者：
Kreyling, Wolfgang G.
中科院分区：
文献类型：
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作者：
Geiser, Marianne;Quaile, Oliver;Kreyling, Wolfgang G.
背景：用于局部或全身治疗的吸入性纳米载体很有前途。金纳米粒子（AuNP）已被广泛认为是候选材料。需要了解它们与肺的相互作用，首先是它们被表面巨噬细胞和上皮细胞的吸收。吸入性肺是特别感兴趣的，因为它们是吸入治疗的主要接受者。因此，我们使用Scnn 1b转基因（Tg）小鼠作为慢性阻塞性肺疾病（COPD）的模型，并比较了吸入的AuNP在表面巨噬细胞和肺组织中的吸收和定位野生型（Wt）mice.Methods：Scnn 1b-Tg和Wt小鼠吸入21 nm AuNP气溶胶2小时。结果：金纳米粒子主要以100 nm的单重态或小团聚体存在。在雾化吸入后0 h，69.2 +/- 4.9%的金纳米粒子是腔，即附着在上皮表面和24.0 +/- 5.9%的巨噬细胞在Scnn 1b-Tg小鼠。在Wt小鼠中，35.3 +/- 32.2%的AuNP位于上皮细胞上，58.3 +/- 41.4%位于巨噬细胞中。两组管腔AuNP的百分比从0 h到24 h均下降。在24 h时，Scnn 1b-Tg小鼠中15.5 +/- 4.8%的AuNP是管腔内的，21.4 +/- 14.2%在上皮细胞内，63.0 +/- 18.9%在巨噬细胞中。在Wt小鼠中，9.5 +/- 5.0%的AuNP是管腔内的，2.2 +/- 1.6%在上皮细胞内，82.8 +/- 0.2%在巨噬细胞中。BAL-macrophage分析显示在0 h时Wt动物和在24 h时Scnn 1b-Tg小鼠中增强的AuNP摄取，证实了Scnn 1b-Tg小鼠中AuNP的效率较低和清除延迟。在Wt和Scnn 1b-Tg小鼠中，吸入的AuNP迅速结合到肺泡上皮。与Wt小鼠相比，Scnn 1b-Tg小鼠表面巨噬细胞对AuNP的摄取效率较低，同时肺泡I型上皮细胞对颗粒的内化率较高。这可能促进Scnn 1b-Tg小鼠中AuNP的深度易位，包括增强上皮靶向。这些结果表明AuNP纳米载体递送作为COPD中肺泡上皮细胞和巨噬细胞的治疗靶向的成功策略。
Background: Inhalative nanocarriers for local or systemic therapy are promising. Gold nanoparticles (AuNP) have been widely considered as candidate material. Knowledge about their interaction with the lungs is required, foremost their uptake by surface macrophages and epithelial cells.Diseased lungs are of specific interest, since these are the main recipients of inhalation therapy. We, therefore, used Scnn1b-transgenic (Tg) mice as a model of chronic obstructive pulmonary disease (COPD) and compared uptake and localization of inhaled AuNP in surface macrophages and lung tissue to wild-type (Wt) mice.Methods: Scnn1b-Tg and Wt mice inhaled a 21-nm AuNP aerosol for 2 h. Immediately (0 h) or 24 h thereafter, bronchoalveolar lavage (BAL) macrophages and whole lungs were prepared for stereological analysis of AuNP by electron microscopy.Results: AuNP were mainly found as singlets or small agglomerates of 100 nm). At 0 h after aerosol inhalation, 69.2 +/- 4.9% AuNP were luminal, i.e. attached to the epithelial surface and 24.0 +/- 5.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 35.3 +/- 32.2% AuNP were on the epithelium and 58.3 +/- 41.4% in macrophages. The percentage of luminal AuNP decreased from 0 h to 24 h in both groups. At 24 h, 15.5 +/- 4.8% AuNP were luminal, 21.4 +/- 14.2% within epithelial cells and 63.0 +/- 18.9% in macrophages in Scnn1b-Tg mice. In Wt mice, 9.5 +/- 5.0% AuNP were luminal, 2.2 +/- 1.6% within epithelial cells and 82.8 +/- 0.2% in macrophages.BAL-macrophage analysis revealed enhanced AuNP uptake in Wt animals at 0 h and in Scnn1b-Tg mice at 24 h, confirming less efficient macrophage uptake and delayed clearance of AuNP in Scnn1b-Tg mice.Conclusions: Inhaled AuNP rapidly bound to the alveolar epithelium in both Wt and Scnn1b-Tg mice. Scnn1b-Tg mice showed less efficient AuNP uptake by surface macrophages and concomitant higher particle internalization by alveolar type I epithelial cells compared to Wt mice. This likely promotes AuNP depth translocation in Scnn1b-Tg mice, including enhanced epithelial targeting. These results suggest AuNP nanocarrier delivery as successful strategy for therapeutic targeting of alveolar epithelial cells and macrophages in COPD.