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 × 10−6–5 × 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 β-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.