TOXICOLOGY OF THIOL-CAPPED QUANTUM DOTS OF CADMIUM AND LEAD Research is proposed to elucidate toxicology and pharmacokinetics of thiol-capped CdSe, CdS, PbSe and PbS quantum dots (QDs) in vivo. These QDs exhibit bright, photo-stable and size-tunable fluorescence. Further, their ultrafine particles (2-6 nm) show dimensional similarity with proteins. Thus, they are potential alternatives to traditional fluorescent dyes as optical probes in biomedical imaging and diagnostics, provided that the safety issues associated with heavy metals (Cd and Pb) are resolved. Capping with thiols is a potential avenue to render these hazardous QDs safe for biomedical applications, but the safety and pharmacokinetics of capped QDs are not known. To be viable, the QDs must be stable in vivo and eliminated completely from the body. Our hypothesis is that thiol-capped QDs will not be totally innocuous when used for therapeutic purposes as they readily bind to biological molecules and bioaccumulate in the body. The cap will be removed in vivo resulting in the exposure of the whole body to hazardous QDs and heavy metals. To elucidate the lexicological consequences of exposure, rats will be exposed to thiol-capped QDs (2-6 nm) intravenously (IV) with and without irradiating the QDs by UV light. The specific aims of the project are to: 1) determine the elimination rate of QDs from the body;2) determine the cap stability by measuring content of metal ions and QDs in the urine and blood;3) determine the accumulation limits in critical organs, including the heart, liver, lungs, kidney, brain and the bones;4) determine the toxic effects and localization of QDs;5) statistically evaluate cap stability, bioaccumulation profile and toxic effects associated with QD type, dose and UV light exposure;and 6) develop a computational model of structure/toxicity to predict the factors contributing most to toxicity. Various analytical chemistry and toxicology methods will be used in combination with UV-visible, plasma source emission/mass spectroscopy and fluorescence microscopy to characterize QDs in the organs. The results of this project will advance our understanding of the safety and toxicology of thiol-capped QDs of CdSe, CdS, PbSe and PbS. Successful completion of the project will contribute greatly to achieving the overall goal of RCMI at JSU to increase the pool of highly trained minority professionals in environmental health and nanotoxicology research through competitive programs.