Use of lanthanide-grafted inorganic nanoparticles as effective contrast agents for cellular uptake imaging.
The improvement of commonly used Gd3+ -based MRI agents requires the design of new systems with optimized in vivo efficacy, pharmacokinetic properties, and specificity. To design these contrast agents, two parameters are usually considered: increasing the number of coordinated water molecules or increasing the rotational correlation time by increasing molecular weight and size. This has been achieved by noncovalent or covalent binding of low-molecular weight Gd3+ chelates to macromolecules or polymers. The grafting of these high-spin paramagnetic gadolinium chelates on metal oxide nanoparticles (SiO2, Al2O3) is proposed. This new synthetic strategy presents at least two main advantages: (1) a high T1-relaxivity for MRI with a 275% increase of the MRI signal and (2) the ability of nanoparticles to be internalized in cells. Results indicate that these new contrast agents lead to a huge reconcentration of Gd3+ paramagnetic species inside microglial cells. This reconcentration phenomenon gives rise to high signal-to-noise ratios on MR images of cells after particle internalization, from 1.4 to 3.75, using Al2O3 or SiO2 particles, respectively. The properties of these new particles will be further used to get new insight into gene therapy against glioma, using microglial cells as vehicles to simultaneously transport a suicide gene and contrast agents. Since microglia are chemoattracted to brain tumors, the presence of these new contrast agents inside the cells will lead to a better MRI determination of the in vivo location, shape, and borders of the tumors. These Gd3+-loaded microglia can therefore provide effective localization of tumors by MRI before applying any therapeutic treatment. The rate of carcinoma remission following a suicide gene strategy is also possible.
Voisin
Pierre
P
Résonance Magnétique des Systèmes Biologiques, UMR CNRS 5536, 146 rue Léo Saignat, F-33076 Bordeaux cedex France.
Ribot
Emeline Julie
EJ
Miraux
Sylvain
S
Bouzier-Sore
Anne-Karine
AK
Lahitte
Jean-François
JF
Bouchaud
Véronique
V
Mornet
Stéphane
S
Thiaudière
Eric
E
Franconi
Jean-Michel
JM
Raison
Lydia
L
Labrugère
Christine
C
Delville
Marie-Hélène
MH
D000537:Aluminum Oxide / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D019786:Gadolinium DTPA / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011437:Propylamines / Q000737:chemistry; D012821:Silanes / Q000737:chemistry; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry
D003287:Contrast Media; D011437:Propylamines; D012821:Silanes; C088294:3-aminopropyltrimethoxysilane; D012822:Silicon Dioxide; D019786:Gadolinium DTPA; D000537:Aluminum Oxide