Study of the MR relaxation of microglia cells labeled with Gd-DTPA-bearing nanoparticles.

Therapies involving cells as vehicles need to visualize in situ the trafficking of the cells concerned. This cellular imaging can be driven by cell contrast agent-based nanoparticle internalization and non-invasive MRI (magnetic resonance imaging) detection. Here, microglial cells, that would transport a suicide gene to a glioma, were incubated for different times, with various concentrations of silica nanoparticles on which numerous Gd-DTPA were grafted. The goal of this study was to investigate the repartition of cell-associated particles. MRI was used to quantitatively follow the particle uptake process. Fluorescence microscopy images showed that, although most of the nanoparticles were internalized, some remained adsorbed on the extracellular membrane surface. The cells were then submitted to various treatments: glycine to release bound nanoparticles and/or ultrasound to destroy the cell membranes. The R(1) relaxation rates were measured at 4.7 T. R(1) was maximal for 4 h of incubation, decreased after 8 h and remained stable for the 24 following hours. The magnetic resonance signal of ultrasonicated and glycine-treated cells made it possible to quantify the loss of bound nanoparticles after 8 h. Nevertheless, this release did not prevent cell detection since the internalized nanoparticles are enough concentrated to visualize the labeled cells even after 4 days of cell growth. These results highlight the compartmentalization of nanoparticles in microglia and the evolution of the MR signal of the labeled cells. This study could be of importance to interpret in vivo the MR signal changes that could occur after administration of such nanoparticle-labeled cells in therapeutic strategies

Use of lanthanide-grafted inorganic nanoparticles as effective contrast agents for cellular uptake imaging

The improvement of commonly used Gd3+-based MRI agents requires the design of new systems with optimized in ViVo efficacy, pharmacokinetic properties, and specificity. To design these contrast agents, two parameters are usually considered: increasing the number of coordinated water molecules or increasing the rotational correlation time by increasing molecular weight and size..