Investigation of the differential cytotoxicity of oxide nanoparticles using zebrafish model

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1134468 PunnooseThis NSF award by the Environmental Health and Safety of Nanotechnology program supports work by Professor Alex Punnoose at Boise State University along with collaborators Professors Jeffrey A. Greenwood and Robert Tanguay at Oregon State University to investigate the cytotoxicity of oxide semiconductor nanoparticles using zebrafish as a model system. Thousands of nanotechnology-enabled consumer products are already available on the market and the annual revenue from such products is approaching several trillion dollars. Many semiconductor oxides, such as zinc oxide, at all size ranges (including nanoscale) are currently labeled as "generally recognized as safe" substances by the Food and Drug Administration. However, in vitro experiments by Professor Punnoose's group employing human immune cells have recently demonstrated that zinc oxide nanoparticles display significant cytotoxicity, raising concerns about the environmental safety and health impact of oxide nanoparticles in general. The observed cytotoxicity varies with cell type, and cancer cells showed the strongest effect. Based on these results, this project undertakes detailed in vivo investigations of the cytotoxicity of a panel of commonly used semiconducting oxides such as tin(IV) oxide, cerium(IV) oxide and copper(II) oxide using zebrafish, a more relevant model system for cytotoxicity evaluation. Furthermore, the cell specific cytotoxic response of zinc oxide nanoparticles to cancerous cells observed so far using in vitro studies will be investigated in vivo by injecting fluorescent dye labeled human cancer cells into 48 hour-old transgenic zebrafish, and by noninvasively monitoring the tumor cell invasion, metastasis and pathological angiogenesis. Finally, roles of the various physicochemical properties of oxide nanoparticles in their cytotoxic behavior will be investigated. Based on this information, careful materials engineering approaches will be employed to develop new design rules (i) to remove unwanted toxicity of oxide nanoparticles to normal healthy zebrafish making them safer nanomaterials and (ii) to improve the selectivity and cytotoxicity of any oxide nanoparticles that display selective cancer cell killing so that they can be developed as potential anti-cancer agents. This project will provide research opportunities for several graduate, undergraduate and high school students. Results from the proposed research will be integrated into several existing courses, and a graduate level seminar in the area of nano-bio research will be introduced to educate students and local community about related emerging fields such as nanotechnology, nanotoxicology and nanomedicine.