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 ( Mon Y) 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, Mon Y and its gadolinium complex Mon Y(Gd) aggregate in aqueous solution to give ellipsoidal micelles with a ratio between the micellar axes of ≈1.7 and an aggregation number N agg of ≈30. There are no differences in the aggregation behavior of Mon Y and Mon Y(Gd), which indicates that the presence of metal ions, and therefore the reduction of the net charge, does not influence the aggregation behavior. When Mon Y or Mon Y(Gd) are blended with dioleoyl phosphatidylcholine (DOPC), the aggregation behavior is dictated by the tendency of DOPC to give liposomes. Only when the amount of Mon Y or Mon Y(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 Å, whereas cryogenic transmission electron microscopy images show that the diameter of the liposomes ranges from ≈50 to 150 nm. Self‐assembling micelles of Mon Y(Gd) present high relaxivity values ( r 1p =15.03 m M −1   s −1 ) for each gadolinium complex in the aggregate. Liposomes containing Mon Y(Gd) inserted in the DOPC bilayer at a molar ratio of 20:80 present slightly lower relaxivity values ( r 1p =12.7 m M −1   s −1 ), independently of their internal or external position in the liposome.