title: High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-beta-cyclodextrin.
abstract: Nanosized contrast agents have great potential in magnetic resonance molecular imaging applications for clinical diagnosis. This study proposes new nanoparticles spontaneously formed under mild conditions and composed of a noncovalent adduct between a gadolinium complex, a polymer of beta-cyclodextrin (pbetaCD: MW 1.5 x 10(6) g mol(-1)) and a dextran grafted with alkyl chains (MD). The formation of this supramolecular nanoassembly is based upon a "lock-and-key" recognition process in which the hydrophobic alkyl chains of MD and the adamantyl moieties of macrocyclic Gd(III) chelates are included in the cavities of pbetaCD. The large number of betaCDs contained in the pbetaCD resulted in the formation of 200 nm diameter nanoparticles, each entrapping 1.8 x 10(5) molecules of a low-molecular-weight Gd complex. This system, which exhibits a great relaxivity enhancement (48.4 mM(-1) s(-1), at 20 MHz and 37 degrees C) compared to the Gd(III) chelate itself (5.2 mM(-1) s(-1)), appears to be a promising strategy for the in vivo targeted delivery of Gd(III) complexes. The mechanisms of particle formation, conjugation strategies, and relaxometric characterizations in the field of contrast-enhanced magnetic resonance imaging are discussed.
authors.affiliation: CNRS, UPR 2301, Institut de Chimie des Substances Naturelles (ICSN), Gif-sur-Yvette, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Battistini
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Gref
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Silvia
authors.initials: S
authors.lastname: Fuzerova
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Bernard
authors.initials: B
authors.lastname: Badet
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
mesh_terms: D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D003911:Dextrans; D046911:Macromolecular Substances; D009942:Organometallic Compounds; D011108:Polymers; D047392:beta-Cyclodextrins; D005682:Gadolinium