Date of Award

Summer 2019

Document Type

Open Access Dissertation

Department

Environmental Health Sciences

First Advisor

Jamie R. Lead

Abstract

Nanoscience and nanotechnology have successfully created different nanomaterials, which are defined as materials with at least one dimension between 1-100 nm. This small size gives nanomaterials unique and novel properties compared with bulk material, such as a high surface area, specific mechanical, optical and magnetic properties. These novel properties have stimulated the interest of using nanoparticles in a wide range of consumer products and applications including biomedical, pharmaceutical and drug delivery. Silver and iron oxide nanoparticles attracted more attention commercially due to their antibacterial and magnetic properties, respectively. So, the overall objective of this dissertation was: 1) to examine the implication of well-characterized polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) on human peripheral blood mononuclear cells (PBMCs) at environmentally relevant concentrations, and 2) to investigate the application of iron oxide nanoparticles in fat removal using high-fat diet-fed mice.

AgNPs biological behavior, such as bio-uptake and accumulation, may be affected by their novel properties and they might show different behavior than bulk material and free Ag ions. There is discrepancy in the results as to whether Ag toxicity is caused by nanoparticulate or ions from NP dissolution. In most nanotoxicology studies lack of NP characterization in the relevant exposure media biased the NP dose and toxicity outcome. This study aimed to use in house synthesized and well- characterized PVP-coated AgNPs for investigation of their bio-uptake and toxicity in PBMCs. Synthesis protocol was successful in generating spherical and monodisperse PVP-coated AgNPs. PVP-AgNPs showed more stability in the cell exposure media and no aggregation was observed at any exposed concentrations. AgNPs and silver nitrate (which was used as Ag ion control) indicated the same overall toxicity. Although, after normalizing toxicity to the amount of Ag that was taken up by cells, AgNPs seemed to be more toxic to cells than Ag ions. Our results emphasize the importance of sufficient characterization of nanoparticles in proper exposure media over the exposure time to have a better understanding of nanoparticle behavior and interaction in biological systems for evaluating risk assessment in human exposure.

Iron oxide NPs which are frequently used in nanomedicine, have recently been investigated for oil removal purposes [1]. However, in vitro and in vivo studies on iron oxide NPs toxicity have revealed little consistency of result due to the usage of different NP characterizations and concentrations. In this study we used PVP-coated iron oxide NPs (that were used successfully before for oil removal from aqueous solutions) to remove dietary fat from mice fed with a high-fat diet. Our animal data demonstrated that oral exposure of PVP-coated iron oxide nanoparticles at concentrations up to 20 mg/kg mouse body weight did not cause any significant decrease in the body weight and fat percentage of high-fat diet-fed mice. Although, iron uptake by liver cells and some effects on glucose metabolism in HNP treatment was detected compared to controls. No increase in inflammatory markers were observed using high doses of nanoparticle treated mice compared with high-fat diet. Further studies using different concentrations of NPs with modified surface coatings should be performed to validate our findings. Given the increasing demand for obesity treatments, nanomedicine approaches, coupled with our results, may provide substantial contributions toward progress in this area.

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