Síntese e caracterização de nanopartículas de Au modificadas para contraste multifuncional

Abstract

Diagnostic Imaging Techniques actively contribute for the increase of life expectancy worldwide. They have attractive features and constantly evolve. However, sometimes it is necessary to use contrast agents for a better visualization of the affected areas in certain pathologies. The work developed presents gold nanoparticles coated with a layer of silica that contains modified fluorescent dye and DTPA-Gd3+ (Diethylenetriaminepentaacetate gadolinium III) complex bonded to the surface. Synthetized nanoparticles can play the role as contrast in two of the most used diagnostic imaging techniques: Computed Tomography (CT) and Resonance Magnetic Imaging (MRI). Furthermore, the addition of modified fluorescent dye offers the possibility to monitor the nanoparticles distribution by Fluorescence Imaging (FI). Gold nanoparticles show some advantages compared to the compounds currently used as contrast agents in CT. Modification of fluorescent dye Rhodamine B (RB) by esterification reaction with N-Hydroxysuccinimide (NHS) to obtain Succinimidyl Rhodamine B (SRB) aims to obtain compounds with emission in larger wavelength from more accessible compounds. Coating of gold nanoparticles with a layer of silica aims to provide: i) a suitable surface for complex DTPA-Gd3+ bonding, already in clinical use as MRI exogenous contrast agent; ii) a separation between gold and fluorophore to prevent photobleaching phenomena; iii) to bypass biocompatibility issues. DTPA ligand was modified by silylation with 3-Chloropropyltrietoxysilane (CPTES) in order to get OH groups capable to bond to silica surface. Gold nanoparticles with size of 5-30 nm were synthetized and characterized by Dynamic Light Scattering (DLS). Rhodamine B was modified to obtain Succinimidyl Rhodamine B characterized by Fourier Transformed Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance of Hydrogen 1 and Carbon 13 (1H NMR e 13C NMR), Distortionless Enhancement by Polarization Transfer at 135º (DEPT 135) and Ultraviolet and visible Spectroscopy (UV-vis). The results of coated nanoparticles obtained by DLS suggest the formation of a layer of silica of 3,5 nm (± 6 nm) thick. Modification of DTPA ligand to obtain sylilated DTPA (Syl-DTPA) was characterized by FTIR. Imaging tests by X-ray (mammography) and RMI suggest that synthetized nanoparticles are promising as multifunctional contrast agents.