Covalent functionalization of multi-walled carbon nanotubes with a gadolinium chelate for efficient T1-weighted magnetic resonance imaging

Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non-invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non-ionizing whole-body high field magnetic resonance imaging (MRI) is used to follow the distribution of water-dispersible non-toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd-CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd-CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd-CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd-CNTs is observed, confirming the evidences of other studies using different imaging modalities

The one year fate of iron oxide coated gold nanoparticles in mice

Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate

Water Dispersible Carbohydrate-Coated Ferrite Nanoparticles. Effect of Cobalt Doping in Magneto-Thermal Properties

International audienc

NMR investigation of functionalized magnetic nanoparticles Fe3O4 asT1–T2contrast agents

In this paper, we report the synthesis of size-controlled (6 and 18 nm) monodisperse magnetic iron oxide nanoparticles, from the pyrolysis of iron oxyhydroxide with oleic acid in high temperature solvents. Superconducting Quantum Interface Device (SQUID) measurements revealed that the iron oxide nanoparticles exhibit a superparamagnetic behavior at room temperature. In order to evaluate their potential applications as contrast agents in Nuclear Magnetic Resonance (NMR) imaging, we investigated using 1H NMR spectroscopy (at a magnetic field 4.7 T) the changes in $T_1$ and $T_2$ relaxation times in the colloidal aqueous solution at various concentration of nanoparticles. The following transverse ($r_2$) and longitudinal ($r_1$) relaxivities were found: ($r_2 = 17.85 mM^{-1}s^{-1}, r_1 = 6.90 mM^{-1}s^{-1}$) and($r_2 = 9.20 mM^{-1}s^{-1}, r_1 = 4.30 mM^{-1}s^{-1}$) for nanoparticle sizes of 18 and 6 nm, respectively. These results confirm that the synthesized nanoparticles have both high $r_1$ and $r_2$ relaxivities and thus the capacity for positive or negative contrast enhancement. This effect increaseswith the nanoparticle size. We also developed a new recognition motif of a saccharide type (mannose coating) for targeting biological models (plants) at the tissue and cellular levels in order to track the flow of the water and saccharide (which are the main drivers of plant growth) in NMR imaging. Moreover, we demonstrated that this saccharide motif provides good biocompatibility and biodistribution in a physiological mediu

Covalent functionalization of multi-walled carbon nanotubes with a gadolinium chelate for efficient T1-weighted magnetic resonance imaging

Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non-invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non-ionizing whole-body high field magnetic resonance imaging (MRI) is used to follow the distribution of water-dispersible non-toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd-CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd-CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd-CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd-CNTs is observed, confirming the evidences of other studies using different imaging modalities

Cooperative Organization in Iron Oxide Multi-Core Nanoparticles Potentiates Their Efficiency as Heating Mediators and MRI Contrast Agents

International audienceIn the pursuit of optimized magnetic nanostructures for diagnostic and therapeutic applications, the role of nanoparticle architecture has been poorly investigated. In this study, we demonstrate that the internal collective organization of multi-core iron oxide nanoparticles can modulate their magnetic properties in such a way as to critically enhance their hyperthermic efficiency and their MRI T1 and T2 contrast effect. Multi-core nanoparticles composed of maghemite cores were synthesized through a polyol approach, and subsequent electrostatic colloidal sorting was used to fractionate the suspensions by size and hence magnetic properties. We obtained stable suspensions of citrate-stabilized nanostructures ranging from single-core 10 nm nanoparticles to multi-core magnetically cooperative 30 nm nanoparticles. Three-dimensional oriented attachment of primary cores results in enhanced magnetic susceptibility and decreased surface disorder compared to individual cores, while preserving a superparamagnetic-like behavior of the multi-core structures and potentiating thermal losses. Exchange coupling in the multi-core nanoparticles modifies the dynamics of the magnetic moment in such a way that both the longitudinal and transverse NMR relaxivities are also enhanced. Long-term MRI detection of tumor cells and their efficient destruction by magnetic hyperthermia can be achieved thanks to a facile and nontoxic cell uptake of these iron oxide nanostructures. This study proves for the first time that cooperative magnetic behavior within highly crystalline iron oxide superparamagnetic multi-core nanoparticles can improve simultaneously therapeutic and diagnosis effectiveness over existing nanostructures, while preserving biocompatibility