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1.6 BIOLOGICAL SCIENCES
This study aims to investigate the biological responses induced by silver nanoparticles (AgNP) following oral exposure. The commonality of AgNP in consumer goods highlights the need for a thorough investigation into the interaction with and subsequent responses evoked in living systems following exposure. Firstly, the potential interaction with and effect of biofluid components, namely cholic acid (CA), deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on AgNP toxicity was investigated. Two cell lines corresponding to organs related to the biofluid components, HepG-2 a hepatocellular carcinoma derived from liver tissue and Hep2 an epithelial cell line, were employed. Physicochemical and cytotoxic screening was performed and the ability of biofluid components to modify AgNP cytotoxicity was explored. No alteration to the physicochemical characteristics of AgNP by biofluid components was observed; however their addition resulted in altered AgNP toxicity. Greater reactive oxygen species (ROS) induction was noted in the presence of CA and DCA. UDCA demonstrated no modification of toxicity in HepG-2 cells however significant modification was observed in Hep2 cells. It was concluded that biofluid components can modify AgNP toxicity but is dependent on the biofluid component itself and the location where it acts. As inhalation is the most common route of nanoparticle entry and given the close proximity to the GI tract, the tendency of cross exposure between the two is prevalent. As such the next line of investigation involved the potential toxicity of AgNP to A549 alveolar epithelial carcinoma cells and the influence of a major component of lung surfactant dipalmitoylphosphatidylcholine (DPPC) on toxicity. This follow up investigation revealed that exposure generated low levels of oxidative stress and a reduction in cell viability. While the presence of DPPC caused no influence on viability studies its presence increased ROS formation and significantly modified the inflammatory response generated by AgNP exposure. These findings suggest a possible interaction between AgNP and DPPC causing particles to become more reactive thus increasing oxidative insult and inflammatory response within A549 cells.
The final investigation in this report was on the biological effects of AgNP on the innate immune response of circulating white blood cells. This study determined the ability of AgNP to induce an inflammatory response in THP-1 monocytes by measuring AgNP stimulated gene expression of the pro-inflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). A further study on monocytes extracted from a cohort of blood samples, was carried out to compare the inflammatory response to THP-1 monocytes. Finally ELISAs were performed on supernatants of THP-1 monocyte cultures to test for the activation of pro-IL-1β a key mediator of the inflammasome complex. The findings clearly demonstrate AgNP can significantly up-regulate pro-inflammatory cytokine gene expression in THP-1 and primary human blood monocytes, with IL-1β release by inflammasome involvement indicating AgNP can result in an immunologically active state.
Murphy, A. (2015) An investigation into the biological responses induced following oral exposure to silver nanoparticles. Doctoral Thesis. Technological University Dublin. doi:10.21427/D73K5W