Physicochemical determinants of distribution and fate of nanoparticles following in vivo exposure
EMSL Project ID
30504
Abstract
The risks associated with the use of nanomaterials have been recently under investigation (1) as increasingly more nanosized products are developed and commercialized. The advent of nanotoxicology as a new discipline, dealing with the effects of engineered nanodevices and structures in living organisms has led to a rapid growth in the development of in vitro and in vivo techniques for toxicity assessments. Due to the vast differences between the physical and chemical properties of nanomaterials, each material is able to elicit its own unique biological responses. Therefore, even though certain concepts of toxicity based on their nanosized dimensions may be similar, most nanoparticulate systems should be characterized and investigated for biodistribution and fate in the biological environment individually. For example, even a traditionally inert element like gold (bulk-sized), has been shown to generate a biological response as a nanomaterial. In this study, we propose to investigate the tissue distribution and fate of quantum dot based-silica coated gold-speckled nanocrystals (CdS: Mn /ZnS-SiO2-Au) following single intravenous exposures of Male Sprague-Dawley rats. More specifically, we aim to study the effect of varying surface charges (positive, negative and zero) and shape (spherical and higher aspect ratio nanorods) on the biodistribution behavior. By screening multiple organs and tissues at different time points after exposure, it will be possible to determine the charge dependent distribution of the engineered nanocrystals and their fate inside the organism. This information will aid in establishing exposure guidelines and designing biocompatible nanoparticles. These studies will therefore directly contribute to EMSL mission in supporting environmental research, and target EMSL Biological Interactions and Dynamics Science Theme by focusing on the Impact of Nanotechnology on Living Systems. Our studies will therefore be guided by the working hypothesis that the charge of particle determines its tissue distribution and fate within the organism and that nanoparticles are likely to be distributed at remote locations from the site of exposure. The inherent fluorescent (excitation 355 nm and emission 600 nm) signature of the quantum dot core of the engineered gold-speckled silica coated nanocrystals will be used to track the particles inside the tissues and organs, within the organism. It is uncertain whether particles will be distributed diffusely across the various organs and tissues, where single particles might be present within a field of view, or whether particles will be present as aggregates. Therefore, we will take advantage of EMSLs unique capabilities in particle size, surface charge measurements and high sensitivity fluorescence imaging to screen tissue sections taken at different time intervals post exposure. Using multichannel fluorescence imaging, and TEM, it will be possible to determine the target of the particles and their fate within the organism, organ or cell. By identifying the in vivo distribution and fate of particles with different physicochemical properties it will be possible to delineate charge-dependent potential toxicity or biocompatibility and aid in formulating preventative approaches. In addition, these data will be applied to development of a physiologically based pharmacokinetic model for nanoparticles.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2008-08-15
End Date
2011-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Hinderliter PM, KR Minard, G Orr, WB Chrisler, BD Thrall, JG Pounds, and JG Teeguarden. 2010. "ISDD: A Computational Model of Particle Sedimentation, Diffusion and Target Cell Dosimetry for In Vitro Toxicity Studies." Particle and Fibre Toxicology 7(November):Article No. 36. doi:10.1186/1743-8977-7-36
Teeguarden JG, PM Hinderliter, G Orr, BD Thrall, and JG Pounds. 2007. "Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments." Toxicological Sciences 95(2):300-312. doi:10.1093/toxsci/kfl165
Waters KM, LM Masiello, RC Zangar, BJ Tarasevich, NJ Karin, RD Quesenberry, S Bandyopadhyay, JG Teeguarden, JG Pounds, and BD Thrall. 2009. "Macrophage Responses to Silica Nanoparticles are Highly Conserved Across Particle Sizes." Toxicological Sciences 107(2):553-569.