Nanoparticle Disruption of Cell Function
Andrij Holian, Ph.D.
Carbon nanoparticles (CNPs) are finding increased use in commercial, diagnostic, clinical and other applications. CNP production is anticipated to greatly increase and there is evidence of CNP formation by anthropogenic activity. However, evidence of their potential toxicity is also increasing and respiratory exposure is considered one route of exposure. A number of studies have now demonstrated that manufactured CNP (single walled carbon nanotubes (SWNT), multi-walled carbon nanotubes (MWNT) and to a lesser extent C60 carbon spheres (C60CS)) all cause pulmonary toxicity ranging from inflammation, granuloma formation, fibrosis and airway changes. Macrophages are considered potential targets of CNP in the Jung that may contribute to pathologic outcomes. In vitro toxicity of these particles has been demonstrated with a suggested rank order of potency most often SWNT> MWNT> C60CS. Although reports of nanoparticle toxicity are increasing, the results are often difficult to correlate since the sources (and compositions) and methods of suspension are different for CNP, and often only one particle type is examined. Furthermore, the mechanism(s) by which these uniquely hydrophobic particles are acting is unknown. Based on the unusual physical properties and size of the carbon nanoparticles, as well as our preliminary results with SWNT, MWNT and C60CS, we postulate that CNP are causing membrane disruption leading to changes in macrophage function contributing to lung inflammation. Furthermore, the different sizes of the CNPs may contribute to the rank order of potency and effects.
In order to test these hypotheses and gain new information on mechanisms of action we propose the following goals.
The results of these studies will provide important new information regarding the roles that different CNP sources, suspension (disaggregation) protocols and CNP types have on membrane disruption. In addition, the studies will provide information on the mechanism of action in membranes how that translates to alterations of macrophage function.