Critical determinants of uptake and translocation of nanoparticles by the human pulmonary alveolar epithelium.
Critical determinants of uptake and translocation of nanoparticles by the human pulmonary alveolar epithelium.
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DOI：
10.1021/nn505399e
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发表时间：
2014-11-25
期刊：
影响因子：
17.1
通讯作者：
Tetley, Teresa D.
中科院分区：
文献类型：
--
作者：
Thorley, Andrew J.;Ruenraroengsak, Pakatip;Potter, Thomas E.;Tetley, Teresa D.
操纵纳米材料的尺寸和表面特性的能力使它们成为改善药物输送和功效的有前途的载体。吸入是一种理想的给药途径，因为纳米材料优先沉积在肺泡区域，肺泡区域是药物吸收的大表面积。然而，迄今为止，人们对颗粒穿过肺泡上皮层移位的机制知之甚少。在这里，我们表明，人肺泡 I 型上皮细胞内化纳米颗粒，而肺泡 II 型上皮细胞则不会，并且纳米颗粒跨上皮单层易位，但无法穿透细胞之间的紧密连接，从而排除了细胞旁易位。此外，使用 siRNA，我们证明 50 nm 纳米颗粒主要通过被动扩散进入并存在于细胞质中，而 100 nm 纳米颗粒主要通过网格蛋白和小窝蛋白介导的内吞作用进入并在内体中发现。纳米颗粒的功能化增加了它们的吸收并增强了表面活性剂的结合，从而进一步促进了吸收。因此，我们证明肺上皮的摄取和易位是由肺泡I型上皮细胞控制的，此外，我们强调了在设计新的纳米药物以改善药物向肺部的输送时应考虑的许多因素。
The ability to manipulate the size and surface properties of nanomaterials makes them a promising vector for improving drug delivery and efficacy. Inhalation is a desirable route of administration as nanomaterials preferentially deposit in the alveolar region, a large surface area for drug absorption. However, as yet, the mechanisms by which particles translocate across the alveolar epithelial layer are poorly understood. Here we show that human alveolar type I epithelial cells internalize nanoparticles, whereas alveolar type II epithelial cells do not, and that nanoparticles translocate across the epithelial monolayer but are unable to penetrate the tight junctions between cells, ruling out paracellular translocation. Furthermore, using siRNA, we demonstrate that 50 nm nanoparticles enter largely by passive diffusion and are found in the cytoplasm, whereas 100 nm nanoparticles enter primarily via clathrin- and also caveolin-mediated endocytosis and are found in endosomes. Functionalization of nanoparticles increases their uptake and enhances binding of surfactant which further promotes uptake. Thus, we demonstrate that uptake and translocation across the pulmonary epithelium is controlled by alveolar type I epithelial cells, and furthermore, we highlight a number of factors that should be considered when designing new nanomedicines in order to improve drug delivery to the lung.
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影响因子：
10
作者：
Gasser M;Wick P;Clift MJ;Blank F;Diener L;Yan B;Gehr P;Krug HF;Rothen-Rutishauser B
通讯作者：
Rothen-Rutishauser B
影响因子：
4.9
作者：
Endres, Thomas;Zheng, Mengyao;Kissel, Thomas
通讯作者：
Kissel, Thomas
DOI：
10.1073/pnas.98.2.646
发表时间：
2001-01-16
影响因子：
11.1
作者：
O'Hare, MJ;Bond, J;Jat, PS
通讯作者：
Jat, PS
影响因子：
5.8
作者：
Liu, He;Gong, Tao;Zhang, Zhirong
通讯作者：
Zhang, Zhirong
影响因子：
10.8
作者：
Novak, Pavel;Shevchuk, Andrew;Korchev, Yuri E.
通讯作者：
Korchev, Yuri E.