Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications


  • Special issue devoted to contributions presented at the E-MRS Symposium C “Peptide-based materials: from nanostructures to applications”, 7–11 June 2010, Strasbourg, France.


New mixed nanoparticles were obtained by self-aggregation of two amphiplic monomers. The first monomer (C18)2L5-Oct contains two C18 hydrophobic moieties bound to the N-terminus of the cyclic peptide octreotide, and spaced from the bioactive peptide by five units of dioxoethylene linkers. The second monomer, (C18)2DTPAGlu, (C18)2DTPA or (C18)2DOTA, and the corresponding Gd(III) complexes, contains two C18 hydrophobic moieties bound through a lysine residue to different polyamino-polycarboxy ligands: DTPAGlu, DTPA or DOTA. Mixed aggregates have been obtained and structurally characterized by small angle neutron scattering (SANS) techniques and for their relaxometric behavior. According to a decrease of negative charges in the surfactant head-group, a total or a partial micelle-to-vesicle transition is observed by passing from (C18)2DTPAGlu to (C18)2DOTA. The thicknesses of the bilayers are substantially constant, around 50 Å, in the analyzed systems. Moreover, the mixed aggregates, in which a small amount of amphiphilic octreotide monomer (C18)2L5-Oct (10% mol/mol) was inserted, do not differ significantly from the respective self-assembled systems. Fluorescence emission of tryptophan residue at 340 nm indicates low mobility of water molecules at the peptide surface. The proton relaxivity of mixed aggregates based on (C18)2DTPAGlu(Gd), (C18)2DTPA(Gd) and (C18)2DOTA(Gd) resulted to be 17.6, 15.2 and 10.0 mM−1 s−1 (at 20 MHz and 298K), respectively. The decrease in the relaxivity values can be ascribed to the increase in τM (81, 205 and 750 ns). The presence of amphiphilic octreotide monomer exposed on mixed aggregate surface gives the entire nanoparticles a potential binding selectivity toward somatostatin sstr2 receptor subtype, and these systems could act as MRI target-specific contrast agent. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.