Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan.
Chem Res Toxicol. 2011 Feb 18;24(2):253-61. doi: 10.1021/tx100376n. Epub 2011 Jan 24.
The cornea is a potential route of exposure and drug administration for nanoparticles. In this work, we use noninvasive two-photon microscopic imaging to study the distribution and permeability pathway of CdSe/ZnS core/shell quantum dots (QDs) capped with three different functional groups through the cornea. With no additional staining, the two-photon image clearly discloses that fluorescent QDs penetrate and reside within the interlamellar space of second harmonic generating collagenous stroma when the corneal epithelium barrier is injured. An in vitro cytotoxicity test using bovine corneal stromal cells incubated individually with all three kinds of QDs indicates that the cell viability decreases significantly as the QD concentration and incubation period increased. The results also show that the specific QDs influence corneal stromal cell viability up to a significant magnitude of 50% under a relatively low concentration (5-20 nM) and short exposure period (24-48 h). Furthermore, two-photon imaging shows that QDs can be retained within the cornea up to 26 days in an in vivo mouse model. On the basis of our in vivo and in vitro data, we conclude that QDs can penetrate and be retained within cornea long enough to cause consequential cytotoxicity, under the circumstance in which the corneal epithelium barrier is injured. Since corneal abrasion is quite a common situation in daily life, our work raises public attention to the potential risk of eye exposure to nanoparticles.
角膜是纳米粒子暴露和给药的潜在途径。在这项工作中,我们使用非侵入性双光子显微镜成像来研究通过角膜用三种不同官能团封端的 CdSe/ZnS 核/壳量子点(QD)的分布和渗透途径。无需额外染色,双光子图像清晰地揭示了当角膜上皮屏障受损时,荧光 QD 穿透并存在于二次谐波产生的胶原基质的层间空间中。用三种 QD 分别孵育牛角膜基质细胞的体外细胞毒性试验表明,随着 QD 浓度和孵育时间的增加,细胞活力显著降低。结果还表明,在相对较低的浓度(5-20 nM)和较短的暴露时间(24-48 h)下,特定的 QD 会导致角膜基质细胞活力显著降低 50%。此外,双光子成像显示,在体内小鼠模型中,QD 可在角膜中保留长达 26 天。基于我们的体内和体外数据,我们得出结论,在角膜上皮屏障受损的情况下,QD 可以穿透并在角膜中保留足够长的时间,从而导致 consequential cytotoxicity。由于角膜擦伤在日常生活中很常见,我们的工作引起了公众对眼睛暴露于纳米粒子的潜在风险的关注。