Gd-DOTA Functionalized Silica Nanoparticles for Magnetic Resonance Imaging: Influence of Particle Size, Surface Loading and Surface Charge on Relaxivity

Size dependent properties of spherical, non-porous and monodisperse silica nanoparticles (SNPs)with diameters of about 15, 50 and 130 nm were examined for their application as potential contrast agents (CAs) for magnetic resonance imaging (MRI). The NPs were covalently functionalized with two different lanthanoid(III) (Ln = Gd) DOTA chelate complexes via an aminopropyl linker.[1] Surface loading with Gd-chelates was varied by repeating the coupling procedure resulting in Gd-loading of up to 125 mmol/g NP. The surface charge was modified by acetylation of remaining amino groups following the primary coupling reaction with Gd-chelates. Additionally, stability studies for reconjugated nanoparticles with high payload of Gd complexes were carried out with respect to leaching of complexes from surface and release of free Gadolinium from complexes. Further measurements, like dynamic light scattering (DLS) and Zeta potential measurements were carried out investigating surface interparticle interactions and the influence of surface charges. In order to evaluate an optimal particle size the expected increase in relaxivity due to Gd(III) surface payloading was examined. Longitudinal and transverse relaxation rates (r1 and r2) of the NPs were investigated by MRI at 3 Tesla in agar phantoms. Enhancement of relaxivities (r1 and r2) occured after modification by repeated conjugation with Gd complex and acetyl protection of residual surface amino groups, respectively, resulting in r1 values of up to 4.49×105 mM- 1s-1. A significant strong increase was detected in the transverse relaxivities r2 of the materials as well