Modulation of Qdot Nanoparticle Toxicity By Glutathione in Gcl Transgenic Mice
Terrance Kavanagh, Ph.D.
Recent advances in nanotechnology have produced a new class of fluorescent nanoparticles, semiconductor quantum dots (QDs). These nanometer-sized crystals have unique photochemical and photophysical properties that are not available from either isolated molecules or bulk solids, and consequently have enabled new opportunities in many areas including optoelectronics, anti-counterfeiting inks, and photovoltaics. More recently, the research interest in QDs has shifted toward the life sciences, where material scientists, chemists and biologists are working together to develop these quantum-confined nanocrystals as fluorescent probes for biomedical imaging. Compared with organic dyes and fluorescent proteins, semiconductor QDs offer several unique advantages, such as size- and composition-tunable emission from visible to infrared wavelengths, large absorption coefficients across a wide spectral range, and very high levels of brightness and photostability. High-quality QDs are generally made from group II-VI and -V elements in the chemical periodic table including Cd and Hg, which are toxic heavy metals. Our preliminary results indicate that polymer-protected QDs remain intact in live cells and animals for up to 2-4 months and are non-toxic. But their long term degradation, metabolism, and clearance are still unknown, which will ultimately determine the suitability of QDs for biomedical applications. Furthermore, because QDs intended for applications other than biomedicine will not necessarily be designed with biocompatibility in mind, concerns have been raised regarding potential occupational and environmental exposures to QDs. In this context, we propose to systematically investigate the toxicity of QDs of different chemical compositions. We will focus on QDs that have practical applications in photonics, optics, solar cells, sensors and biomedical imaging. We hypothesize that the colloidal stability and nanomaterial surface properties such as surface ligands and functional groups will affect in vitro and in vivo behavior and toxicity of QDs. In order to address this hypothesis, this application will focus on innovations of nanoparticle synthesis and surface engineering, in vitro toxicity to multiple murine and human cell types, and in vivo toxicity in genetically modified mice. Information gathered from these studies will be valuable in helping to predict the role of various constituent metals on the toxicity of QDs, as well as in the design of cores and coatings that will optimize the desirable properties of these materials while minimizing their adverse health impacts. Such information will be useful in risk assessments of these materials, and thus help to inform regulatory policy making.