Stealth macromolecular platforms for the design of MRI blood pool contrast agents

Mathurin Grogna; Rudi Cloots; André Luxen; Christine Jérôme; Catherine Passirani; Nolwenn Lautram; Jean-F. Desreux; Mike Collodoro; Marie-Claire De Pauw-Gillet; Christophe Detrembleur

doi:10.1039/C1PY00198A

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Polymer Chemistry

Issue 10, 2011

Encompassing all aspects of synthetic and biological macromolecules, and related emerging areas

Impact Factor 5.321 24 Issues per Year

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Stealth macromolecular platforms for the design of MRI blood pool contrast agents

Mathurin Grogna,^a Rudi Cloots,^b André Luxen,^c Christine Jérôme,^a Catherine Passirani,^d Nolwenn Lautram,^d Jean-F. Desreux,^e Mike Collodoro,^f Marie-Claire De Pauw-Gillet^f and Christophe Detrembleur*^a

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Center for Education and Research on Macromolecules (CERM), University of Liège, B6 Sart-Tilman, Liège, Belgium
E-mail: christophe.detrembleur@ulg.ac.be ;
Fax: +32-4-3663497 ;
Tel: +32-4-3663465

Laboratoire de chimie inorganique structurale, University of Liège, B6 Sart Tilman, Liège, Belgium

Cyclotron Research Centre, University of Liège, B6 Sart Tilman, Liège, Belgium

INSERM U 646, 10 Rue A Boquel, Angers, France

Coordination and Radiochemistry, University of Liège, B6 Sart Tilman, Liège, Belgium

Laboratory of Histology-Cytology (GIGA-R), University of Liège, B6 Sart Tilman, Liège, Belgium

Polym. Chem., 2011,2, 2316-2327

DOI: 10.1039/C1PY00198A
Received 05 May 2011, Accepted 09 Jun 2011
First published online 28 Jul 2011

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Abstract
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Stealth macromolecular platforms bearing alkyne groups and poly(ethylene oxide) brushes were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The anchoring of Gd³⁺-chelates bearing an azide group was then carried out by the Huisgen 1,3-dipolar cycloaddition (“click”) reaction in mild conditions, leading to macrocontrast agents for MRI applications. The gadolinium complex is hidden in the PEO shell that renders the macrocontrast agents free of any cytotoxicity and stealth to proteins of the immune system. Relaxometry measurements have evidenced an improved relaxivity of the macrocontrast agent compared to ungrafted gadolinium chelate. Moreover, this relaxivity is further enhanced when the spacer length between the Gd³⁺-chelate and the polymer backbone is shorter, as the result of its decreased tumbling rate. These novel products are therefore promising candidates for MRI applications.

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