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Article Dans Une Revue Organic & Biomolecular Chemistry Année : 2011

Synthesis and physicochemical characterization of new squalenoyl amphiphilic gadolinium complexes as nanoparticle contrast agents.

Mohammad Othman
  • Fonction : Auteur
Didier Desmaële
Patrick Couvreur
Luce Vander Elst
Sophie Laurent
Robert N Muller
  • Fonction : Auteur
Claudie Bourgaux
  • Fonction : Auteur
Estelle Morvan
Thierry Pouget
  • Fonction : Auteur
Sinda Lepêtre-Mouelhi
Ruxandra Gref

Résumé

A family of novel amphiphilic gadolinium chelates was successfully obtained by coupling the hydrophilic DOTA ligand [1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane] to squalenoyl moieties. Thanks to the self-assembling properties of their squalenoyl lipophilic moieties, all these derivatives were able to form, without any adjuvant, micellar or liposome-like supramolecular nanoassemblies, endowed with high relaxivities (r(1) = 15-22 mM(-1) s(-1) at 20 MHz and 37 °C). The remarkably high payloads of Gd(3+) ions reached 10 to 17 wt %. Moreover, one of these derivatives interacted with human serum albumin (HSA) forming mixed micelles, which induced a remarkable increase in relaxivity. Liposome-like structures were obtained when the Gd(3+) complex of DOTA was coupled to two squalene units. These liposomal structures were characterized by a high loading of Gd(3+) (about 74 000 gadolinium ions per particle of 100 nm). The supramolecular architecture of these nano-objects has been investigated by electron microscopy and small-angle X-ray scattering. Squalenoylation of gadolinium derivatives offers a platform to conceive contrast agents (CAs) in mild conditions (no toxic solvents, no surfactants, no energy input). These new amphiphilic gadolinium chelates could also find potential applications in theranostics, by forming mixed systems with other squalenoylated drugs, or to delineate blood vessels owing to the interaction with HSA.

Domaines

Chimie organique
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Dates et versions

hal-00606158 , version 1 (05-07-2011)

Identifiants

Citer

Mohammad Othman, Didier Desmaële, Patrick Couvreur, Luce Vander Elst, Sophie Laurent, et al.. Synthesis and physicochemical characterization of new squalenoyl amphiphilic gadolinium complexes as nanoparticle contrast agents.. Organic & Biomolecular Chemistry, 2011, 9 (11), pp.4367-4386. ⟨10.1039/c1ob00015b⟩. ⟨hal-00606158⟩
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