In vivo detection of magnetic labeled oxidized multi-walled carbon nanotubes by magnetic resonance imaging

Abstract

Functionalized carbon nanotubes (f-CNTs) have been widely used in bio-medicine as drug carriers, bio-sensors, imaging agents and tissue engineering additives, which demands better understanding of their in vivo behavior because of the increasing exposure potential to humans. However, there are limited studies to investigate the in vivo biodistribution and elimination of f-CNTs. In this study, superparamagnetic iron oxides (SPIOs) were used to label oxidized multiwalled carbon nanotubes (o-MWCNTs) for in vivo distribution study of o-MWCNTs by magnetic resonance imaging (MRI). SPIO labeled o-MWCNTs (((SPIO))o-MWCNTs) were prepared by a hydrothermal reaction process, and characterized by TEM, XRD and magnetometer. ((SPIO))o-MWCNTs exhibited superparamagnetic property, excellent biocompatibility and stability. The intravenously injected ((SPIO))o-MWCNTs were observed in liver, kidney and spleen, while the subcutaneously injected ((SPIO))o-MWCNTs could be only detected in sub mucosa. Most of the intravenously injected ((SPIO))o-MWCNTs could be eliminated from liver, spleen, kidney and sub mucosa on 4 d post injection (P.I.). However, the residual o-MWCNTs could induce 30-40% MRI signal-to-noise ratio changes in these tissues even on 30 d P.I. This in vivo biodistribution and elimination information of o-MWCNTs will greatly facilitate the application of f-CNT based nanoproducts in biomedicine. In addition, the magnetic labeling method provides an approach to investigate the in vivo biodistribution and clearance of other nanomaterials.

Suppression of cytokine synthesis in spleen and brain and small changes in c-fos expression in rat brain after intranasal administration of single-walled carbon nanotubes

“…Thus, CNTs were detected in the spleen and liver, but not in the lungs, kidney, and skin when administered intravenously; in this case, hematological or immunological toxicity was not observed [7]. In another study, at the same administration mode, the functional MWCNTs were found in the liver, kidney, and spleen, from which they were eliminated mainly in 4 days [6]. By magnetic resonance imaging, it was shown that, after intravenous injection to rats, SWCNTs are accumulated in the spleen (up to 7 days), liver (up to 2 days), and kidneys (up to 5 days), but not in the lungs and blood [8].…”

“…CNTs can be accumulated in various tissues at different administration modes, but most commonly in the spleen and liver [6][7][8].…”

Molecular Mechanisms, Characterization Methods, and Utilities of Nanoparticle Biotransformation in Nanosafety Assessments

“…[13] However, it is still controversial whether these tissues are damaged. [5,7,8,14,15] ENMs in different organs could be taken into cells through endocytosis, phagocytosis, micropinocytosis, or diffusion. [16,17] After cellular internalization, NPs either assemble in intracellular vesicles (endosomes or lysosomes) or freely distribute in cytoplasm, [18] and a small portion of them (e.g., La 2 O 3 , CuO) may elicit hazard biochemical signals (e.g., oxygen radical generation, [19] cellular redox changes, [20] enzyme inactivation [21] ) and cytotoxicity.…”

“…For the biomedical applications of ENMs, intravenous injection is a conventional route for the administration of nanomedicines or nanosized imaging agents. [9,15] When ENMs in fluids are introduced directly into the vein, the particles may first react with biomolecules in circulation, such as proteins, lipids, and amino acids to form a thin layer binding on surfaces, namely "corona" structures ( Figure 2D). These interactions may influence the circulation times, cellular uptake, immune responses, biodistribution, clearance, and metabolism of ENMs.…”

Nanoparticle Functionalization and Its Potentials for Molecular Imaging

“…Xu et al reported that, simply adding GdCl 3 to the solution mixture containing a carbon source(citrate acid) and passivating agent (ethanediamine) create better MRI agents than DTPA linked Gd particles because of high loading, with its quantum yield efficiency unchanged 42. Li et al worked with multiwalled carbon nanotubes (MWCNTs) of diameter 40–60 nm and showed that those tubes can be oxidized to introduce carboxylic groups on the surface to attach with Fe(III) ions and later link with SPIONs through solvothermal procedures 43. These MWCNTs now can be analyzed through MRI along with fluorescence, therefore giving better details about the in vivo biodistribution and clearance even 30 d after injection.…”