Investigating the impact of gold nanoparticles on pulmonary cells: From 2D to 3D culture systems
Nanomaterials are well-suited for a variety of applications because of their unique properties on the nanoscale. Interest in using gold nanoparticles in biological applications is growing ranging from sensing to cancer therapy due to their tunable sizes and shapes, unique optoelectronic properties, and straightforward surface modification. The advancement of fine-tuning of gold nanoparticle sizes, shapes, and surface chemistry is critical for various applications. However, many of these applications are developed in controlled environments, and not subject to the complex biological systems. Indeed, the interaction between gold nanoparticles and biological systems cannot be predicted by a single physiochemical property of nanoparticles. This interaction comes from an ensemble, combining all nanoparticle physiochemical properties and the complexity of biological systems. As a result, a fundamental understanding of how nanoparticle physiochemical properties influence biological systems is a building block for the foundation of many applications. Chapter 1 will introduce the concept of nanomaterials and their unique properties. Then syntheses and surface modification of gold nanoparticles will be introduced. These include seed-mediated growth of gold nanospheres and nanorods and the control over absolute dimensions of gold nanoparticles. Then the surface modification of gold nanoparticles, including thiol functionalization, and layer-by-layer polyelectrolyte and mesoporous silica coatings are addressed. Finally, challenges of applying nanoparticles in biological systems are discussed. Chapter 2 focuses on controlling absolute lengths and widths of gold nanorods toward tunable longitudinal localized surface plasmon resonance. Precise control over gold nanorod widths less than 10 nm accompanied by increasing gold nanorod lengths was achieved by a seed-mediated growth method. These seed-mediated growth of mini gold nanorods leads to excellent shape percent yields and > 79% of gold ion reduction. We show that liter-scale mini gold nanorod syntheses are reproducible and their dimensions and shape percent yields are comparable to those of a small-scale synthesis. We elucidate the size effect of gold nanorods on cellular uptake and removal in Chapter 3. To correlate how each parameter (width, length, aspect ratio, and dimension) influences endo- and exocytosis, four different seed-mediated growth methods were introduced to prepare four types of rods. We found that a low correlation exists between the cellular uptake of gold nanorods and rod lengths, but there is a negative correlation between the cellular uptake of rods and rod widths in primary human pulmonary artery endothelial cells. We also investigated gold nanorod secretion kinetics in a 10 h interval. At the end of 10 h, > 75% of rods were removed from the cells. The impact of gold nanoparticle aerosols on human airway epithelium differentiation is discussed in Chapter 4. We show how to build a 3-dimentional human lung model cultured at an air-liquid interface. Gold nanosphere aerosols were delivered to the cocultures of primary human pulmonary cells through nebulization to mimic human inhalation. Our lung model shows successful epithelium differentiation regardless of gold nanosphere aerosol exposure. However, changes of inflammatory responses remained after aerosol exposure. In Chapter 5, we conclude the fine-tuning of gold nanorod lengths and widths, the size dependent endo- and exocytosis of gold nanorods in primary human pulmonary artery endothelial cells and the effect of gold nanosphere aerosols on human small airway epithelium differentiation. Finally, applications of mini gold nanorods with tunable plasmonic properties and possible upcoming experiments to elucidate the effect of gold nanoparticle size and surface chemistry on the morphological and molecular changes in a human lung microenvironment are addressed.
gold nanoparticles, seed-mediated growth, mini gold nanorods, large-scale synthesis, endocytosis, exocytosis, primary human pulmonary artery endothelial cells, gold nanoparticle aerosols, 3-dimentional human lung model, air-liquid interface, human airway epithelium differentiation
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign