Department of Medicine, Division of NanoMedicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
ACS Nano. 2012 May 22;6(5):3745-59. doi: 10.1021/nn204671v. Epub 2012 Apr 13.
We investigated and compared nanosize Ag spheres, plates, and wires in a fish gill epithelial cell line (RT-W1) and in zebrafish embryos to understand the mechanism of toxicity of an engineered nanomaterial raising considerable environmental concern. While most of the Ag nanoparticles induced N-acetyl cysteine sensitive oxidative stress effects in RT-W1, Ag nanoplates were considerably more toxic than other particle shapes. Interestingly, while Ag ion shedding and bioavailability failed to comprehensively explain the high toxicity of the nanoplates, cellular injury required direct particle contact, resulting in cell membrane lysis in RT-W1 as well as red blood cells (RBC). Ag nanoplates were also considerably more toxic in zebrafish embryos in spite of their lesser ability to shed Ag into the exposure medium. To elucidate the "surface reactivity" of Ag nanoplates, high-resolution transmission electron microscopy was performed and demonstrated a high level of crystal defects (stacking faults and point defects) on the nanoplate surfaces. Surface coating with cysteine was used to passivate the surface defects and demonstrated a reduction of toxicity in RT-W1 cells, RBC, and zebrafish embryos. This study demonstrates the important role of crystal defects in contributing to Ag nanoparticle toxicity in addition to the established roles of Ag ion shedding by Ag nanoparticles. The excellent correlation between the in vitro and in vivo toxicological assessment illustrates the utility of using a fish cell line in parallel with zebrafish embryos to perform a predictive environmental toxicological paradigm.
我们研究并比较了纳米银球、纳米银片和纳米银丝在鱼类鳃上皮细胞系（RT-W1）和斑马鱼胚胎中的毒性机制，以了解一种具有重要环境意义的工程纳米材料的毒性机制。虽然大多数纳米银颗粒在 RT-W1 中诱导了 N-乙酰半胱氨酸敏感的氧化应激效应，但纳米银片的毒性比其他颗粒形状大得多。有趣的是，虽然银离子释放和生物利用度不能全面解释纳米银片的高毒性，但细胞损伤需要直接的颗粒接触，导致 RT-W1 细胞膜破裂和红细胞（RBC）破裂。尽管纳米银片向暴露介质中释放银的能力较低，但在斑马鱼胚胎中它们的毒性也大得多。为了阐明纳米银片的“表面反应性”，进行了高分辨率透射电子显微镜研究，结果表明纳米银片表面存在高水平的晶体缺陷（位错和点缺陷）。用半胱氨酸进行表面涂层处理，以钝化表面缺陷，结果表明 RT-W1 细胞、RBC 和斑马鱼胚胎的毒性降低。这项研究表明，除了纳米银颗粒的银离子释放所起的作用外，晶体缺陷在纳米银颗粒毒性中也起着重要作用。体外和体内毒理学评估之间的良好相关性表明，使用鱼类细胞系与斑马鱼胚胎平行进行预测性环境毒理学研究的实用性。
