Functionalized single-walled carbon nanotubes containing traces of iron as new negative MRI contrast agents for in vivo imaging

Unité de Pharmacologie Chimique et Génétique et d'Imagerie, Chimie ParisTech, Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, CNRS UMR 8151, Inserm U1022, Paris, F-75270 cedex, France.
Contrast Media & Molecular Imaging (Impact Factor: 2.92). 03/2012; 7(2):153-9. DOI: 10.1002/cmmi.474
Source: PubMed


Single-walled carbon nanotubes (SWCNTs) containing traces of iron oxide were functionalized by noncovalent lipid-PEG or covalent carboxylic acid function to supply new efficient MRI contrast agents for in vitro and in vivo applications. Longitudinal (r(1)) and transversal (r(2)) water proton relaxivities were measured at 300 MHz, showing a stronger T(2) feature as an MRI contrast agent (r(2)/r(1)  = 190 for CO(2) H functionalisation). The r(2) relaxivity was demonstrated to be correlated to the presence of iron oxide in the SWNT-carboxylic function COOH, in comparison to iron-free ones. Biodistribution studies on mice after a systemic injection showed a negative MRI contrast in liver, suggesting the presence of the nanotubes in this organ until 48 h after i.v. injection. The presence of carbon nanotubes in liver was confirmed after ex vivo carbon extraction. Finally, cytotoxicity studies showed no apparent effect owing to the presence of the carbon nanotubes. The functionalized carbon nanotubes were well tolerated by the animals at the dose of 10 µg g(-1) body weight.

Download full-text


Available from: Cyrille Richard, Nov 28, 2014
  • Source
    • "Nevertheless, applying CNTs to several fields of medicine requires detailed studies on their physical properties [6] [7] and an assessment of their toxicity level. A number of studies report the potential use of Single Walled Carbon Nanotubes (SWCNTs) and Multi Walled Carbon Nanotubes (MWCNTs) as both T 1 -based and T 2 -based MRI CAs [8] [9] [10] [11]. Unfortunately, due to the non-standardized synthesis protocols , scientific reports from different sources cannot be collated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In this work, functionalized Multiwall Carbon Nanotubes of specified length and containing well-defined iron particles (O-MWCNT/Fe) were prepared. A significant enhancement in contrast in Magnetic Resonance Imaging was found for the investigated composites. The magnetic characterization revealed the ferromagnetic nature of iron particles embedded within O-MWCNTs. The enhancement of the 1H spin–spin relaxation time of MRI scans using hydrophilic O-MWCNT/Fe as potential contrast agents was estimated for selected dispersive media. Moreover, the cytotoxicity of the hybrids was studied in two cell lines, i.e. cancer cells (HeLa) and fibroblasts (GM07492). The intracellular impact of O-MWCNT/Fes in HeLa cells was observed after staining of selected organelles (nuclei and mitochondria). Significant changes in cell morphology were found for water soluble MWCNT/Fes with diameters above 30 nm.
    Full-text · Article · Jul 2015 · Carbon
  • Source
    • "The contrast was attributed to the presence of iron impurities [21] and the magnetic resonance contrast observed was directly related to their iron content [22]. A range of methods have been used to modify CNTs potentially containing residual iron for MRI application, such as oxidation [23], non-covalent lipid-PEG modification [24], and ionic surfactants modification [25]. Therefore, the combination of polymer coated CNTs (as carriers) and attached metal ions (as contrast components) is expected to be highly suitable for use as MRI contrast agents with improved efficiency, dispersibility, and biocompatibility. "
    [Show abstract] [Hide abstract]
    ABSTRACT: An efficient MRI T2-weighted contrast agent incorporating a potential liver targeting functionality was synthesized via the combination of superparamagnetic iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs). Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified with a potential targeting agent, lactose-glycine adduct (Lac-Gly), were subsequently immobilized on the surface of the PDDA-MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low cytotoxicity in vitro to HEK293 and Huh7 cell lines. Enhanced T2 relaxivities were observed for the hybrid material (186 mm(-1) s(-1)) in comparison with the pure magnetic nanoparticles (92 mm(-1) s(-1)) due to the capacity of the MWCNTs to "carry" more nanoparticles as clusters. More importantly, after administration of the composite material to an in vivo liver cancer model in mice, a significant increase in tumor to liver contrast ratio (277%) was observed in T2 weighted magnetic resonance images.
    Full-text · Article · Oct 2013 · Biomaterials
  • [Show abstract] [Hide abstract]
    ABSTRACT: Single-walled carbon nanotubes (SWNTs) are special nano-materials which exhibit interesting physical and chemical properties, presenting new opportunities for biomedical research and applications. In this study, we have successfully adopted a novel strategy to chemically functionalize SWNTs with polyethylenimine (PEI) through purification, oxidation, amination and polymerization, which were then bound by DSPE-PEG2000-Maleimide for further conjugation with the tumor targeting NGR (Cys-Asn-Gly-Arg-Cys-) peptide via the maleimide group and sulfhydryl group of cysteine, and finally hTERT siRNA was loaded to obtain a novel tumor targeting siRNA delivery system, designated as SWNT-PEI/siRNA/NGR. The results showed that SWNT-PEI/siRNA/NGR could efficiently cross cell membrane, induced more severe apoptosis and stronger suppression in proliferation of PC-3 cells in vitro. Furthermore, in tumor-bearing mice model the delivery system exhibited higher antitumor activity due to more accumulation in tumor without obvious toxicity in main organs. The combination of RNAi and near-infrared (NIR) photothermal therapy significantly enhanced the therapeutic efficacy. In conclusion, SWNT-PEI/siRNA/NGR is a novel and promising anticancer system by combining gene therapy and photothermal therapy.
    No preview · Article · Oct 2012 · Biomaterials
Show more