Peptide derivatized lamellar aggregates as target-specific MRI contrast agents.
The relaxivity behaviour and the structural characterization of new supramolecular aggregates (bilayer structures and micelles) obtained by combining two different amphiphilic monomers are reported. One monomer, (C18)(2)DTPAGlu-Gd, contains a very stable gadolinium complex, and the other, DSPE-PEG(2000)-CCK8, contains the bioactive CCK8 peptide. Samples that contained only DSPE-PEG(2000)-CCK8, or up to 50 % (C18)(2)DTPAGlu-Gd, aggregated as double-layer structures (lamellar aggregates) with a thickness of approximately 80-100 A, as evaluated by SANS measurement and Cryo-TEM imaging. A transition to micelle formation was observed when the amount of (C18)(2)DTPAGlu-Gd in the aggregate was increased. These were rod-like micelles approximately 40 A in radius and >200 A in length. The proton relaxivities for both lamellar aggregates and rod-like micelles were the same (17.2 mM(-1) s(-1)), although the values were the results of different combinations of local and global contributions. The in vitro target selectivity of aggregates that contained the CCK-8 peptide was demonstrated by using nuclear medicine techniques.
Tesauro
Diego
D
Department of Biological Sciences, CIRPeB University of Naples, Federico II and IBB CNR, Via Mezzocannone 16, Naples, Italy.
Accardo
Antonella
A
Gianolio
Eliana
E
Paduano
Luigi
L
Teixeira
José
J
Schillén
Karin
K
Aime
Silvio
S
Morelli
Giancarlo
G
D002766:Cholecystokinin / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008823:Micelles; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D003287:Contrast Media; D046911:Macromolecular Substances; D008823:Micelles; D009942:Organometallic Compounds; D010446:Peptide Fragments; D010455:Peptides; C410885:cholecystokinin 8; D002766:Cholecystokinin; D005682:Gadolinium