Graduate Thesis Or Dissertation
 

Nanoparticle features and their relative influence on biological responses

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  • Nanoparticles (NPs), defined as materials having at least one dimension (height, width, diameter) in the nanoscale, are increasingly being incorporated into a wide variety of products and are replacing traditional bulk materials in many applications. This is because they can be more efficacious, more sustainable, and can have unique characteristics as compared to their bulk counterparts. NPs can be synthesized from and contain any element or combination thereof from the periodic table. Their size, shape, composition, and surface functionality can be manipulated to form innumerable combinations. Because of their increasing use, there is a critical need to determine what features of NPs drive their biological responses in order to inform their application and potential risk to human health and the environment. In this dissertation, I present evaluations of NP-biological responses for three types of NPs: functionalized crystalline nanocellulose, copper-based nanomaterials, and differentially shaped and charged Au NPs. In all assessments, I used the embryonic zebrafish and a comparative approach to determine which NP features were driving the biological responses I observed. For crystalline nanocellulose, I found that the surface functionalization altered the pH of the exposure media, leading to toxicity that could be rescued by pH adjustment. Copper-based nanomaterial toxicity correlated with the NP’s ability to generate reactive oxygen species rather than other characterized features of dissolution, agglomerate size, surface charge, or uptake. Toxicity of Au NPs was dependent on their shape, which was confirmed through dosimetry and a collaboration that determined a potential mechanism of membrane interaction of each shape tested. These findings provide evidence that nanomaterial features drive biological responses and suggest a mechanistic basis for what was observed. These relationships can be used in rational design of new nanomaterials for specific applications and to build a case for the risk of existing materials. There still exists a data gap for mechanistic determination of nanomaterial toxicity; however, the challenges associated with assaying nanomaterial toxicity must be addressed to continue advancement of their mechanistic evaluation.
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  • Ongoing Research
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  • 2019-03-23 to 2021-04-24
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