Effects of nanoparticle functionalization, shape & size on lung function & inflammation

With the rise of nanoparticle use in commercial products, industry, and medicine, there is a need to better understand the consequences of nanoparticle exposure. Due to their nano-scale size, the lung is a primary route of exposure. To study the effects of nanoparticle functionalization, shape and size on the lung, an organ-level toxicological approach was taken. To achieve an organ-level approach, respiratory mechanics were first evaluated using a murine model. Following ventilation, bronchoalveolar lavage was performed to obtain cells and lung lining fluid for cytokine, protein, and lipid analysis. Lastly, the lungs were harvested for assessment of tissue structure and immunohistochemistry. The collection of these endpoints allowed for a more complex approach that relates both molecular and physiological endpoints, which provides the foundation for more translational work to be done that addresses both environmental and occupational exposure risks to the public concerning nanomaterials. The data provided within this thesis validates that the primary driving factors in organ level respiratory response to nanoparticle exposure are: core composition (metal v. carbon), zeta potential, shape, and host inflammatory state. These factors affect injury and inflammation, surfactant composition and lung function. Overall, this work outlines how nanoparticle biophysics alter both lung function and inflammation.Ph.D.Includes bibliographical referencesby Danielle Joy Botelh