Nanoparticles (NPs), particles defined by their size in a single dimension (1-100 nm), are being increasingly incorporated into commercial and industrial products due to their high surface area to volume ratio that gives them unique properties, such as optical tunability and higher reactivity than their bulk counterparts. NPs can be designed for a diverse variety of applications through tuning of their physicochemical properties: core composition, surface chemistry, size, and shape. The unique properties of NPs make them of great interest in the medical field, where silver and gold nanoparticles are being increasingly employed as antimicrobials and nanomedicines. As humans are being actively and intentionally exposed to these NPs, understanding how the various physiochemical properties affect the nanoparticle-biological interactions (NBIs) and drive toxicity is of critical importance. In this thesis, I address some of the physiochemical properties of interest for both silver and gold nanoparticles.
Silver nanoparticles (AgNPs) are currently used in a variety of industrial and commercial products due to their well understood antimicrobial properties. However, a major confounding factor of all AgNP research is the contribution that silver ions (Ag+) dissolution has to the toxicity of the particles. Here I employ the use of differentially coated silver nanoparticles of two geometries, spherical and triangular plate, to assess the effects that shape has on AgNP toxicity while the confounding factor of Ag+ dissolution is controlled for. A suite of 10 AgNPs, five varieties of surface coatings for each the spherical and triangular plate AgNPs, were monitored over a 4-week period to fully understand their differential surface shielding and protection from Ag+ dissolution. Toxicity of the particles was assessed in vivo using the embryonic zebrafish model. This suite of NPs provides an improved platform to use when assessing the biological interactions of AgNPs.
Gold nanoparticles (AuNPs) are being engineered into pharmaceuticals and show great potential in cancer therapies. Due to their growing use in nanomedicines and intentional exposure to humans, it is of critical importance to understand the effects that changing a single physiochemical property can have on the toxicity of AuNPs. Gold and uncoated AuNPs are well studied and understood to be non-toxic; however, when a surface coating is applied, an essential component of all AuNP nanomedicine applications, AuNPs show altered properties and sometimes elicit toxicity. Here I utilized AuNPs coated with a lipid bilayer at three different sizes, 5 nm, 10 nm, and 20 nm. These AuNPs were tested at three different levels of biological organization (biomimetic lipid-monolayer, in vitro, and in vivo) to fully assess the differential NBIs that drive their toxicity.
The studies presented in this thesis provide a better understanding of the NBIs that drive the toxicity of gold and silver NPs. This work provides insight into how we can modify the physiochemical properties of gold and silver NPs to increase their effectiveness while also improving safety.