Nanostructures based on monoolein or diolein and amphiphilic gadolinium complexes as MRI contrast agents

Highly ordered two or three dimensional mesophases in aqueous solution could be usefully obtained by using monoolein (MO) or diolein (DO) monomers. Nanostructures (also indicated as nanoparticles, NPs) of MO or DO containing different amounts (1%, 5%, 10% and 20%) of the synthetic amphiphilic gadolinium complex (C18)₂DTPA(Gd) have been prepared and characterized for their relaxometric and structural behaviors. The nanostructure is found in the 110-200 nm range for all investigated systems, while the presence of the gadolinium containing monomer produces a partial loss of the cubic symmetry, as shown by Cryo-TEM images of NPs doped with 10% w/w of (C18)₂DTPA(Gd). Gadolinium containing nanostructures display high relaxivity values (in the 10-15 mM^-1 s^-1 range at 25° and 20 MHz, with a further increase at 37 °C for DO based NPs), and interesting relaxometric properties for their possible use as MRI contrast agents. NPs containing 10% w/w of (C18)₂DTPA(Gd) (MO3-NPs and DO3-NPs) have been also derivatized by introducing 3% wt of (C18)₂-Peg₃₀₀₀-FA to obtain targeted aggregates (MO3-NP-FA, DO3-NP-FA). A preferential uptake efficiency of DO3-NP-FA in IGROV-1 cells with respect to DO-NPs without folic acid is observed, especially when cells are incubated with low concentrations of nanostructures or at short incubation times, thus indicating its potential use as a target-selective delivery system for MRI contrast agents on tumor cells overexpressing the folate receptor.