On Nano-Bio Interactions: Investigation of Biological Impacts Induced by Nanomaterials & Biocoronas

The ascension of nanomaterials in the past decade for sensing, imaging, and delivery platforms in the biomedical fields is attributable to their unique physiochemical properties. It is understood that upon incubation with biological media, pristine nanomaterials will inherit a biological identity through the adsorption of biomolecules onto the material surfaces. The attached biomolecules, also known as the biocorona, can govern the extent of toxicity of the xenobiotic nanomaterial; in some cases, the biocorona can impede toxicity, while in other cases, it can exacerbate nanomaterial lethality. Yet, there is still an enormous knowledge gap regarding how nano-sized materials interact with biomolecules and impact biological systems.In this dissertation, the toxicological profile of 40 engineered nanomaterials were assessed in mammary epithelial cells, as detailed in Chapter 1. From this collection, a subset were chosen for further investigation which are detailed in the following chapters. Tungsten disulfide nanosheets were further evaluated in Chapter 2 for their toxicity in lung epithelial cells. Additionally, the mechanism of cell death and impact on the mitochondria were assessed following cellular exposure to tungsten disulfide nanosheets. Since this material was passivated with a surfactant there was no formation of biocorona and thus, toxicity observed was due to the material itself. In Chapter 3, there is a transition into evaluating the toxicity of reduced graphene oxide nanosheets by modulating their surface chemistry with the formation of protein corona. Specifically, reducing the surfactant concentration on reduced graphene oxide nanosheets permitted the adsorption of larger quantities of proteins. Moreover, characterization of the protein corona correlated with the measured biological impacts. In Chapter 4, the lipid and protein corona, also known as the biocorona, were extracted from digested food-grade titanium dioxide nanomaterials for characterization. The bioinformatic profile corroborates previous findings our collaborators observed in a tri-culture small intestinal epithelial model. Lastly, the biocorona from digested polyethylene-based nanoplastics were extracted and characterized in Chapter 5. The lipid and protein profile from the nanoplastics’ biocorona also correlated with the biological impacts observed in the tri-culture model of gastrointestinal cells. This work utilizes analytical chemistry and molecular biology techniques to gauge nanomaterial toxicity, isolate and characterize biocoronas, and identify correlations between biocoronas and biological impacts observed in lung, gastrointestinal and mammary cells. The approach taken in this work adds fundamental knowledge in understanding the impact nanomaterials have on different biological systems as well as the complexities of biocorona formation for future developments of safer nanotechnologies for biological applications