Colloidal Upconverting Nanoparticle Systems for Integration in Targeting, Therapeutics and Imaging Applications

• Main Author: Naccache, Rafik
• Format: Others
• Published: 2012
• Online Access: http://spectrum.library.concordia.ca/974619/4/Naccache_PhD_F2012.pdf; Naccache, Rafik <http://spectrum.library.concordia.ca/view/creators/Naccache=3ARafik=3A=3A.html> (2012) Colloidal Upconverting Nanoparticle Systems for Integration in Targeting, Therapeutics and Imaging Applications. PhD thesis, Concordia University.

The synthesis and surface modification of sodium gadolinium fluoride (NaGdF4:Er3+/Tm3+, Yb3+) nanoparticles were investigated for potential integration in biological applications. These nanoparticles are poised to replace conventional fluorophores in targeting, imaging and therapeutic applications. The latter possess several shortcomings ranging from photobleaching to requirements for ultraviolet (UV) excitation. In contrast, these nanoparticles are optically robust and may be excited using a near infrared (NIR) light source, which can be converted to UV, visible or NIR light via upconversion. Near infrared light is advantageous as it offers greater tissue penetration depth relative to UV or visible light and does not harm cells. Colloidal upconverting nanoparticles were synthesized using thermal decomposition. Synthetic parameters such as reaction temperature (280-320 C), time (30-180 min) and precursor addition rates (0.5 2.5 mL/min) were used to tailor the nanoparticle morphology, crystal phase (cubic or hexagonal) and particle size (10-80 nm). Integration of these nanoparticles in biological applications requires dispersibility in aqueous media. Hence several strategies such as silica shell coating and ligand exchange were carried out to render the nanoparticles hydrophilic. Orthogonal surface functionalization with amino and azido silane reagents was carried out on silica coated nanoparticles allowing for surface decoration using a cancer targeting folic acid derivative and a cis-platinum precursor therapeutic agent. The folate derivative was functionalized to the nanoparticle surface using "click" chemistry via surface N3 groups, while the cis-platinum derivative formed a coordination bond with the surface NH2 groups in a one-pot, one-step approach. The nanoparticle system was tri modal with targeting, imaging and therapeutic capacities. These luminescent upconverting NaY(Gd)F4:Tm3+/Yb3+ nanoparticles were investigated as novel contrast agents in magnetic resonance imaging. Hydrophilic citrate capped colloidal nanoparticles showed strong T1 enhancement effects. Positive contrast enhancement was observed at Gd3+ host concentrations as low as 5 mol%. The 5 nm sized nanoparticles produced similar contrast enhancement to current clinical gadolinium chelates with the added advantage that toxic Gd3+ leaching is not a concern as the ions are tightly bound in the crystal. These nanoparticles have been developed into multimodal systems, which may be used in cancer diagnostic and therapeutic applications as well as in whole body magnetic and optical imaging.