In vivo imaging of transport and biocompatibility of single silver nanoparticles in early development of zebrafish embryos
In vivo imaging of transport and biocompatibility of single silver nanoparticles in early development of zebrafish embryos
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DOI：
10.1021/nn700048y
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发表时间：
2007-09-01
期刊：
影响因子：
17.1
通讯作者：
Xu, Xiao-Hong Nancy
中科院分区：
文献类型：
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作者：
Lee, Kerry J.;Nallathamby, Prakash D.;Xu, Xiao-Hong Nancy
在单纳米粒子分辨率下实时研究纳米材料在早期胚胎发育中的转运和生物相容性，可以为了解纳米材料在体内的输送和作用提供新的知识，并为胚胎发育中的分子转运机制提供新的见解。在这项研究中，我们直接表征了单个纳米银颗粒进入活体模型系统(斑马鱼胚胎)的转运过程，并实时研究了它们对早期胚胎发育的影响。我们设计了高纯度和稳定的(不聚集和无光分解)纳米颗粒，并开发了单纳米颗粒光学和体内测试来支持这项研究。我们发现，单个银纳米颗粒(5-46 nm)通过绒毛膜孔道进入和传出胚胎，并表现出布朗扩散(非主动传输)，其在绒毛膜空间内的扩散系数(3×10(-9)cm(2)/S)类似于在卵水中的扩散系数(7.7X10(-8)cm(2)/S)。相比之下，纳米颗粒被困在CPC和胚胎的内部质量中，显示出有限的扩散。在每个发育阶段的胚胎内以及在正常发育、畸形和死亡的斑马鱼中都观察到了单个的银纳米颗粒，表明银纳米颗粒的生物相容性和毒性以及在斑马鱼中观察到的畸形类型高度依赖于银纳米颗粒的剂量，临界浓度为0.19 nM。胚胎中纳米颗粒的被动扩散和积累的速度可能是剂量依赖性异常的原因。与其他化学物质不同，单个纳米颗粒可以在发育中的胚胎内以纳米空间分辨率直接成像，为揭开导致异常的相关途径提供了新的机会。
Real-time study of the transport and biocompatibility of nanomaterials in early embryonic development at single-nanoparticle resolution can offer new knowledge about the delivery and effects of nanomaterials in vivo and provide new insights into molecular transport mechanisms in developing embryos. In this study, we directly characterized the transport of single silver nanoparticles into an in vivo model system (zebrafish embryos) and investigated their effects on early embryonic development at single-nanoparticle resolution in real time. We designed highly purified and stable (not aggregated and no photodecomposition) nanoparticles and developed single-nanoparticle optics and in vivo assays to enable the study. We found that single Ag nanoparticles (5-46 nm) are transported into and out of embryos through chorion pore canals (CPCs) and exhibit Brownian diffusion (not active transport), with the diffusion coefficient inside the chorionic space (3 x 10(-9) cm(2)/S)similar to 26 times lower than that in egg water (7.7 X 10(-8) cm(2)/s). In contrast, nanoparticles; were trapped inside CPCs and the inner mass of the embryos, showing restricted diffusion. Individual Ag nanoparticles were observed inside embryos at each developmental stage and in normally developed, deformed, and dead zebrafish, showing that the biocompatibility and toxicity of Ag nanoparticles and types of abnormalities observed in zebrafish are highly dependent on the dose of Ag nanoparticles, with a critical concentration of 0.19 nM. Rates of passive diffusion and accumulation of nanoparticles in embryos are likely responsible for the dose-dependent abnormalities. Unlike other chemicals, single nanoparticles can be directly imaged inside developing embryos at nanometer spatial resolution, offering new opportunities to unravel the related pathways that lead to the abnormalities.