Interaction of Nanomaterials with Biological Systems: From Inhalation of Multi-Walled Carbon Nanotubes to the Treatment of Kidney Stones

Abstract

Nanomaterials are widely used in the electronics, automotive, medical, and industries. As usage increases, we need to better understand the health effects of human exposure to these unique nanomaterials. Multi-walled carbon nanotubes (MWCNTs) are nanomaterials that are becoming increasingly common in next-generation technologies. Occupational inhalation of MWCNTs, is of particular concern. The high surface area per unit mass of MWCNTs provides a relatively large surface area for protein adsorption. The resulting protein “corona” dictates the subsequent biological response to these nanomaterials. Our goal is to understand how MWCNTs interact with the protein environment of the lung including bronchoalveolar lung fluid (BALF), albumin, which is the most abundant protein present in BALF, and inhaled allergens. House dust mite (HDM) allergens, known to trigger of allergic airway diseases, particularly asthma, are of specific interest. The coronas formed by these biomolecules were characterized for individual proteins and proteins in combination. We found that der p 2, a protein associated with human allergic responses to HDM, dominates the composition of coronas following subsequent exposures to lung fluid proteins.To better understand the biological implications of HDM adsorption on MWCNTs (HDM-MWCNT), we evaluated the proteolytic activity of the allergens found in interactions between HDM and MWCNTs. HDM contains cysteine and serine proteases, enzymes that break down protein, that contribute to the pathophysiology of allergic airway diseases when active. We compared the active enzyme activity in free HDM, a mixture of HDM and MWCNTs, and HDM-MWCNT. We also compared the active enzyme concentration of trypsin and papain coronas on MWCNTs and polystyrene nanoparticles (PS NPs). The results should that proteases adsorbed on to the surface of the nanomaterial are less active than in free enzymes. This suggests the activity of proteases is inhibited when adsorbed onto MWCNTs and PS NPs compared to the activity of free proteases. Interactions between lung fluid proteins and MWCNTs was further investigated by measuring the concentration of albumin, as representative protein for lung fluid, on the surface of pristine, purified and functionalized MWCNTs. In order to understand how MWCNT compositional and surface modifications can affect the protein corona, we measured the concentration of albumin protein coronas as a function of initial albumin concentration. We found that each type of MWCNT displayed a different relationship between the concentration of the protein corona and the initial concentration. This implies that MWCNT purification and functionalization affect the interactions between lung fluid proteins and MWCNTs. Nanomaterials also have potential to advance medical treatments. In this work, we aim to characterize an ITO@SiO2 nanofluid to mitigate thermal damage to surrounding tissues during kidney stone laser lithotripsy treatment. We characterized the stability of ITO@SiO2 in solution and after being exposed to extreme laser pulses. The nanoparticles were unharmed after laser treatment. This was proven by measuring the concentrations of tin and indium in the supernatant. There were no significant traces of tin and indium that would indicate that ITO@SiO2 nanoparticles disintegrated. We also evaluated the cytotoxicity of bare ITO and ITO@SiO2 nanoparticles at 0.25 wt% and found that neither variant posed a high risk to cell viability. Overall, these results indicate that an 0.25 wt% ITO@SiO2 nanofluid would not pose a significant health risk to cells during laser lithotripsy.