Micelles obtained by aggregation of gemini surfactants containing the CCK8 peptide and a gadolinium complex

Two gemini surfactants, [C18CysL5CCK8]2 and [C18CysDTPAGlu]2, containing, respectively, the CCK8 peptide and the DTPAGlu chelating agent or its gadolinium complex have been prepared by linking lipophilic chains through a disulfide bond between two cysteine residues. The two surfactants aggregate in water solution forming pure or mixed micelles, with a critical micellar concentration in the 5 9 10-6–5 9 10-5 mol kg-1 range, as measured by fluorescence spectroscopy. As indicated by small-angle neutron scattering, the shape and size of the micelles are influenced by the temperature: increasing temperature leads to progressive reduction of the size of the supramolecular aggregates. Cylindrical structures found at lower temperatures (10–40 C) evolve into ellipsoidal micelles at 50–80 C. Furthermore, the surface-exposed CCK8 peptide changes its conformation above a transition temperature of approximately 45 C, going from a beta-sheet to a random-coil structure, as indicated by circular dichroism measurements. The mixed aggregate obtained by coaggregation of the two gemini-based amphiphilic compounds, [C18CysDTPAGlu(Gd)]2 and [C18CysL5CCK8]2 in 70:30 molar ratio, represents the first example of a peptide-containing gemini surfactant as a potential target-selective contrast agent in MRI. In fact, it presents a high relaxivity value of the gadolinium complex, 21.5 mM-1 s-1, and the CCK8 bioactive peptide exposed on the external surface is therefore capable of selective targeting of the cholecystokinin receptors