عنوان

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

Number

TLets665765

Title Proper

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

General Material Designation

[Thesis]

First Statement of Responsibility

Shuwaikan, Mohammed Salem

Name of Publisher, Distributor, etc.

University of Birmingham

Date of Publication, Distribution, etc.

2015

Dissertation or thesis details and type of degree

Thesis (Ph.D.)

Text preceding or following the note

2015

Text of Note

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.

RA Public aspects of medicine

Shuwaikan, Mohammed Salem

University of Birmingham

Electronic name

p

[Thesis]

276903

a

Y