Selective targeting and thermal destruction of live cells using antibody functionalised gold nanoparticles

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Precious metal nanoparticles have attracted considerable interest on account of their actual or potential applications in chemical, biological or medical analyses, and for their applications in various new types of optical devices or systems. These particles can be engineered to absorb light at a particular wavelength and they can also be chemically functionalised to bind to target cells. Active targeting of the gold particles to the site of a disease can be achieved, in principle, by attaching a suitable antibody to the surface of the gold. Localised heating arises when the affected tissue is irradiated with a laser tuned to the plasmon resonance of the nanoparticle because some of the incident laser light is converted to heat in the particle, which then flows out of the nanoparticle into the target cell. This principle is currently being explored overseas as the basis of a novel form of n1edical treatment for cancer. In this thesis, I extend this concept to develop a method for selectively killing different cellular targets. I report how gold nanoparticles, either spherical or rod-shaped, were functionalised with specific antibodies so that they would selectively attach to particular target cells: murine macrophage cells and tachyzoites of the protozoan parasite Toxoplasma gondii. Following this, the cells were exposed to defined wavelengths and low intensities of continuous laser irradiation from a HeNe laser or a solid state diode laser. Cell viability was determined using nucleic stain dye. Exposure of target cells to specific bioconjugated gold nanoparticles resulted in the highest number of cell death compared with other treatments. In addition, another useful result, independent of the actual process of photothermal therapy, is described in this thesis. This involves the attachment of gold nanoparticle-antibody conjugates to Toxoplasma gondii tachyzoites, which clearly reduced their infection of host cells. Therefore, the research described provides both for an exciting and novel possibility for in vivo killing of any type of target cells using photothermal therapy and for a means to decrease host cell invasion by an intracellular parasite in the body.
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