Phosphonium-functionalised gold nanoparticles for mitochondria targeted therapeutics.

The work presented in this thesis demonstrates that triarylphosphoniopropyl-thiosulfate zwitterions and w-thioacetylpropyl(triphenyl)phosphonium salts can be used to prepare cationic, water-soluble gold nanoparticles with mean core sizes in the range of 2.5-5 nm. Phosphonium-functionalised gold nanoparticles have been characterised by a number of techniques including NMR, LDI-MS, SIMS, XPS, TGA, ICP-MS, MALDI-MS and TEM.Cytotoxicity studies illustrated that phosphonium ligands are relatively non-toxic to human prostate cancer cells and therefore can be used as a delivery vector to delivery gold nanoparticles specifically to the site of the mitochondria for other therapeutic applications such as photothermal therapy. Cellular uptake studies of phosphonium ligands by MALDI-MS showed that they are rapidly taken-up by cells within ten minutes.Phosphonium-functionalised gold nanoparticles are soluble in biological media which is of great importance for cell biology studies. Initial photothermal therapy studies demonstrated that the gold nanoparticles responds specifically to a green light excitation source (510-550 nm) which overlaps the surface plasmon resonance band of the phosphonium-functionalised gold nanoparticles at 525 nm. Preliminary data also showed that phosphonium-functionalised gold nanoparticles can selectively induce apoptosis in cells followed by irradiation, this was confirmed by Hoechst and caspase-3 staining. Quantification studies of phosphonium-functionalised gold nanoparticles by ICP-MS illustrated that these nanoparticle have good uptake in cells (above 75%). TEM data confirmed that phosphonium-functionalised gold nanoparticles are taken-up by human prostate cancer cells and are localised in the mitochondria.