Turdalieva Aizat, Solandt Johan, Shambetova Nestan, Xu Hao, Blom Hans, Brismar Hjalmar, Zelenina Marina, Fu Ying
Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, SE-106 91 Stockholm, Sweden.
AstraZeneca R&D, SE-431 83 Mölndal, Sweden.
PLoS One. 2016 Feb 25;11(2):e0149915. doi: 10.1371/journal.pone.0149915. eCollection 2016.
Lung epithelial cells are extensively exposed to nanoparticles present in the modern urban environment. Nanoparticles, including colloidal quantum dots (QDs), are also considered to be potentially useful carriers for the delivery of drugs into the body. It is therefore important to understand the ways of distribution and the effects of the various types of nanoparticles in the lung epithelium. We use a model system of liquid-covered human airway epithelial Calu-3 cell cultures to study the immediate and long-term effects of repeated deposition of colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs on the lung epithelial cell surface. By live confocal microscope imaging and by QD fluorescence measurements we show that the QD permeation through the mature epithelial monolayers is very limited. At the time of QD deposition, the transepithelial electrical resistance (TEER) of the epithelial monolayers transiently decreased, with the decrement being proportional to the QD dose. Repeated QD deposition, once every six days for two months, lead to accumulation of only small amounts of the QDs in the cell monolayer. However, it did not induce any noticeable changes in the long-term TEER and the molecular morphology of the cells. The colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs could therefore be potentially used for the delivery of drugs intended for the surface of the lung epithelia during limited treatment periods.
肺上皮细胞广泛暴露于现代城市环境中存在的纳米颗粒。包括胶体量子点(QDs)在内的纳米颗粒也被认为是将药物输送到体内的潜在有用载体。因此,了解各种类型的纳米颗粒在肺上皮中的分布方式及其影响非常重要。我们使用液体覆盖的人气道上皮Calu-3细胞培养模型系统,来研究胶体3-巯基丙酸包覆的CdSe-CdS/ZnS核-多壳量子点在肺上皮细胞表面重复沉积的即时和长期影响。通过实时共聚焦显微镜成像和量子点荧光测量,我们发现量子点透过成熟上皮单层的渗透非常有限。在量子点沉积时,上皮单层的跨上皮电阻(TEER)短暂下降,下降幅度与量子点剂量成正比。每六天重复量子点沉积,持续两个月,导致细胞单层中仅积累少量量子点。然而,它并未引起长期TEER和细胞分子形态的任何明显变化。因此,胶体3-巯基丙酸包覆的CdSe-CdS/ZnS核-多壳量子点在有限的治疗期内可能潜在地用于递送针对肺上皮表面的药物。