Structural and Relaxometric Characterization of Peptide Aggregates Containing Gadolinium Complexes as Potential Selective Contrast Agents in MRI

The structural and relaxometric characterization of a novel class of supramolecular aggregates, as potential tumor-specific contrast agents in magnetic resonance imaging (MRI), is reported. The aggregates are based on a new monomer with an upsilon shape (MonY) that contains, in the same molecule, all three fundamental tasks that are required: 1) a hydrophobic moiety that allows the formation of supramolecular aggregates; 2) the bioactive CCK8 peptide for target recognition; and 3) a chelating agent able to give stable gadolinium complexes. As indicated by dynamic light scattering and small-angle neutron scattering (SANS) measurements, MonYand its gadolinium complex MonY(Gd) aggregate in aqueous solution to give ellipsoidal micelles with a ratio between the micellar axes of 1.7 and an aggregation number Nagg of 30. There are no differences in the aggregation behavior of MonYand MonY(Gd), which indicates that the presence of metal ions, and therefore the reduction of the net charge, does not influence the aggregation behavior.When MonYor MonY(Gd) are blended with ioleoyl phosphatidylcholine (DOPC), the aggregation behavior is dictated by the tendency of DOPC to give liposomes. Only when the amount of MonYor MonY(Gd) is higher than 20% is the coexistence of liposomes and micelles observed. The thickness d of the bilayer is estimated by SANS to be 35-40 :, whereas cryogenic transmission electron microscopy images show that the diameter of the liposomes ranges from 50 to 150 nm. Self-assembling micelles of MonY(Gd) present high relaxivity values (r1p=15.03 mm1 s1) for each gadolinium complex in the aggregate. Liposomes containing MonY(Gd) inserted in the DOPC bilayer at a molar ratio of 20:80 present slightly lower relaxivity values (r1p=12.7 mm1 s1), independently of their internal or external position in the liposome.