In Vivo Imaging of Transport and Biocompatibility of Single Silver Nanoparticles in Early Development of Zebrafish Embryos

Kerry J. Lee†§, Prakash D. Nallathamby†§, Lauren M. Browning†, Christopher J. Osgood‡ and Xiao-Hong Nancy Xu†*
† Department of Chemistry and Biochemistry
‡ Department of Biological Sciences, Old Dominion University, Norfolk, Virginia 23529
ACS Nano, 2007, 1 (2), pp 133–143
DOI: 10.1021/nn700048y
Publication Date (Web): September 28, 2007
Copyright © 2007 American Chemical Society
* Address correspondence to xhxu@odu.edu., §

These authors contributed equally to this work

Biochemical Methods

Abstract

Abstract Image

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 × 10−9 cm2/s) 26 times lower than that in egg water (7.7 × 10−8 cm2/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.

Keywords:

biocompatibility; diffusion; embryos; in vivo imaging; silver nanoparticle; single-nanoparticle optics; toxicity; transport; zebrafish
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History

  • Published In Issue September 28, 2007
  • Article ASAPSeptember 28, 2007
  • Received: May 30, 2007
    Accepted: September 4, 2007

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