Investigation of the uptake, co-localisation, biological effects, and toxicity mechanism(s) of carboxyl-modified polystyrene nanoparticles (COO-PS-NPs) onto human bronchial epithelial (BEAS-2B) cells

Shuwaikan, Mohammed Salem (2015). Investigation of the uptake, co-localisation, biological effects, and toxicity mechanism(s) of carboxyl-modified polystyrene nanoparticles (COO-PS-NPs) onto human bronchial epithelial (BEAS-2B) cells. University of Birmingham. Ph.D.

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Abstract

Carboxyl-modified polystyrene nanoparticles (COO-PS-NPs) have many potential applications, for example drug-delivery systems, but their toxicity remains poorly assessed. In the current study, characterisation, uptake and toxicity of two sized COO-PS-NPs in cultured BEAS-2B lung epithelial cells were investigated.
The 20nm sized COO-PS-NPs tended to aggregate heavily in the cell culture media yielding larger aggregates, in contrast the 100nm COO-PS-NPs were stable. Electron and confocal microscopy demonstrated that COO-PS-NPs rapidly accumulate in vesicle-like structures within cells and fluorescent organelle co-staining showed the presence of 20nm COO-PS-NPs in mitochondria and the 100nm COO-PS-NPs in Golgi apparatus. Cellular studies revealed that COO-PS-NPs cause GSH depletion and induce ROS generation resulting in oxidative stress. Studies in a cell-free system showed that COO-PS-NPs directly deplete levels of GSH in solution. Size- and concentration-dependent DNA strand breaks (by comet assay) were also observed and both 20nm and 100nm COO-PS-NPs induced caspases-3/7 activation in a Ca2+ independent manner, however a significant decrease in cell viability was observed only at high concentrations of 20nm COO-PS-NPs.
In summary, this \(in\) \(vitro\) study demonstrated that toxicity of the 20nm COO-PS-NPs is mediated by oxidative stress after co-localisation to the mitochondria and that further studies are needed to assess the safety of COO-PS-NPs.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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