title: A top-down synthesis route to ultrasmall multifunctional Gd-based silica nanoparticles for theranostic applications.
abstract: New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd(3+) chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd(3+) by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, (29)Si solid-state NMR, (1)H NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r1 of 11.9 s(-1)  mM(-1) per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd(3+) is strongly chelated to DOTAGA (complexation constant logβ110 =24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.
authors.affiliation: Laboratoire de Physico-Chimie des Matériaux Luminescents, UMR 5620 CNRS-Université Claude Bernard Lyon 1, 69622 Villeurbanne Cedex, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Mignot
authors.forename: Charles
authors.initials: C
authors.lastname: Truillet
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.forename: Cédric
authors.initials: C
authors.lastname: Louis
authors.forename: Franck
authors.initials: F
authors.lastname: Denat
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boschetti
authors.forename: Laura
authors.initials: L
authors.lastname: Bocher
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gloter
authors.forename: Odile
authors.initials: O
authors.lastname: Stéphan
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Antoine
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
authors.forename: Dominique
authors.initials: D
authors.lastname: Luneau
authors.forename: Ghenadie
authors.initials: G
authors.lastname: Novitchi
authors.forename: Leandro Carlos
authors.initials: LC
authors.lastname: Figueiredo
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: de Morais
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonneviot
authors.forename: Belen
authors.initials: B
authors.lastname: Albela
authors.forename: François
authors.initials: F
authors.lastname: Ribot
authors.forename: Luk
authors.initials: L
authors.lastname: Van Lokeren
authors.forename: Isabelle
authors.initials: I
authors.lastname: Déchamps-Olivier
authors.forename: Françoise
authors.initials: F
authors.lastname: Chuburu
authors.forename: Gilles
authors.initials: G
authors.lastname: Lemercier
authors.forename: Christian
authors.initials: C
authors.lastname: Villiers
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Duc
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roux
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
mesh_terms: D003287:Contrast Media / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D061089:Radiotherapy, Image-Guided; D012822:Silicon Dioxide / Q000737:chemistry*; D012833:Siloxanes / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013373:Substance P / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D012833:Siloxanes; C513199:substance P, 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid-arginyl(1)-; D013373:Substance P; C030581:gadolinium oxide; D012822:Silicon Dioxide; D005682:Gadolinium