Peptides and Gd complexes containing colloidal assemblies as tumor-specific contrast agents in MRI: physicochemical characterization.
The aggregation behavior of an amphiphilic supramolecular system, with potential application as a tumor-specific magnetic resonance imaging contrast agent, has been studied in detail by dynamic light scattering, small-angle neutron scattering and cryotransmission electron microscopy. The system was constituted of mixed aggregates formed by an anionic unimer containing the DTPAGlu, a chelating agent for the paramagnetic Gd(3+) ion, and an uncharged unimer containing the bioactive peptide CCK8, capable of directing the assembly toward tumor cells. Mixed aggregates formed by both unimers, and in the case of the DTPAGlu unimer with the chelating agent as free base or as Gd(3+) complex, have been investigated. A number of interesting features of the aggregation behavior were revealed: at physiological pH, micelles and bilayer structures were present, whereas upon decreasing solution pH or increasing ionic strength, the formation of bilayer structures was favored. On the basis of the above observations, the aggregating mechanism has been elucidated by considering the screening effect on intra- and interaggregate electrostatic repulsions.
Vaccaro
Mauro
M
Department of Chemistry, University of Naples Federico II, Naples, Italy.
Accardo
Antonella
A
D'Errico
Gerardino
G
Schillén
Karin
K
Radulescu
Aurel
A
Tesauro
Diego
D
Morelli
Giancarlo
G
Paduano
Luigi
L
D003287:Contrast Media / Q000494:pharmacology*; D020285:Cryoelectron Microscopy; D004058:Diffusion; D005682:Gadolinium / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008027:Light; D008051:Lipid Bilayers; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D012542:Scattering, Radiation; D055672:Static Electricity; D013501:Surface-Active Agents
D003287:Contrast Media; D007477:Ions; D008051:Lipid Bilayers; D008823:Micelles; D010455:Peptides; D013501:Surface-Active Agents; D005682:Gadolinium