The restoration of vascular function in murine vessels, ex vivo, using ceria nanoparticles

Tye, Emily Si Lyn (2016) The restoration of vascular function in murine vessels, ex vivo, using ceria nanoparticles. Masters by Research thesis (MSc), Manchester Metropolitan University.

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Abstract

Nanoparticles show an exciting opportunity within the medical field, such as in diagnostics or therapeutics, due to their capacity to be surface modified and loaded with dyes and drugs. Current clinical applications of nanoparticles include localisation in tumour cells for cancer therapy, delivery of nucleic acids and viral therapies such as HIV vaccination. An exciting area of nanomedicine is using nanotechnology to target inflammatory and chronic diseases that involve the generation of reactive oxygen species (ROS). Cerium provides excellent anti-ROS properties and its effect as a nanoparticle needs to be established. The clinical application of nanoparticles often requires an entry point, one of which is intravenously done. Once injected into the bloodstream, the endothelial cells that line the blood vessel are one of the first sites of exposure, and because endothelial cells are important modulators of vascular function, the influence of silica and ceria-coated silica nanoparticle uptake on vasodilation and cerium’s anti-ROS properties effect on vasodilation, remains unclear.The aim of the present study was to investigate the influence of silica and ceria-coated silica nanoparticles on vascular function of mouse aortic vessels, ex vivo. Silica, ceria and ceria-coated silica nanoparticles were successfully synthesised and their physicochemical characterisation determined. Their effect on constrictor, and both endothelial dependent and independent dilator responses were assessed, using the organ bath technique and evaluation of uptake was also conducted using TEM. The present study demonstrates two important findings. Firstly, that ceria-coated silica nanoparticles have an improved endothelial-dependent dilatory effect on young mouse aorta, whereas silica nanoparticles alone (C3) showed no detrimental effect on both endothelial-dependent and -independent dilation. Secondly, that ceria-coated silica nanoparticles did not improve dilation in aged aortic vessels, and silica nanoparticles (C3) did not show to have a detrimental effect on dilation, since the dilator component in aged vessels was found to be similar to that in young vessels.