Functionalised silica nanoparticles for biomedical imaging

• Main Author: Percival, Sarah Jane
• Other Authors: Long, Nicholas ; Aboagye, Eric
• Published: Imperial College London 2014
• Subjects: 616.99
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.712818

Magnetic resonance imaging is one of the most widely used diagnostic techniques in the clinic as it affords many of the attributes sought from a non-invasive imaging modality. The main limitation of MRI is its inherent insensitivity, and as a result only large-scale abnormalities can be detected from a scan. With an increasing demand for earlier cancer diagnosis there has been a move towards imaging the molecular biomarkers that are present from the beginning of the disease process. This thesis describes the development of highly fluorinated, silica nanoparticles to actively target cancer cells for imaging by 19F MRI. Silica nanoparticles were prepared, and their size optimised for the molecular imaging application. A method was developed to modify the nanoparticles with the highest possible number of surface amine groups. These amine groups were conjugated to fluorinated PEG chains, each containing six equivalent 19F nuclei, and the resulting particles had a high 19F content. To provide the particles with the properties required for a molecular imaging probe, a tenth of the surface bound 19F PEG chains were conjugated to targeting peptides and the remainder were coupled to stabilising ligands. Using quantitative characterisation techniques each modification step was optimised and the exact composition of the nanoparticles was determined. To complement 19F MRI, fluorophores were incorporated into the particles for optical detection as this modality offered an accessible, sensitive and inexpensive alternative. Several samples were prepared which incorporated fluorophores at different positions throughout the nanoparticle structure. Adding the fluorophores to the nanoparticle surface was found to produce the most sensitive optical probe. The final particles were used for in vitro targeting studies to assess their potential as molecular imaging probes. Preliminary in vitro assays demonstrated that these particles selectively targeted cancer cells in the M21 cell line when compared to a control.