Physicochemical Characterization, and Relaxometry Studies of Micro-Graphite Oxide, Graphene Nanoplatelets, and Nanoribbons

Abstract

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents.

Physicochemical characterization of a novel graphene-based magnetic resonance imaging contrast agent

“…1 Our previous results show that the r 2 /r 1 ratio for water-solubilized GNP solutions is 2.2, which is in the range reported for Mn 2+ -or Gd 3+ -chelate complexes (r 2 /r 1 ∼1.0-2.5) T 1 MRI CAs. 7,8 The ratio is also lower than the iron oxide-functionalized graphene nanoparticles (r 2 /r 1 ∼10) T 2 MRI CAs. 7 Thus, the GNP-Dex formulations would be more suitable as a T 1 MRI CA.…”

“…7 The GNPs were non-covalently functionalized with dextran (technical grade, MW 10,000 Da; Pharmacosmos, Hobaek, Denmark) to synthesize GNP-Dex as follows. GNPs and dextran were mixed in distilled deionized (DDI) water at a 1:10 weight ratio, and bath sonicated for 30 minutes followed by the addition of ammonium hydroxide (NH 4 OH).…”

“…The supernatants were analyzed for the presence of free Mn 2+ ions using sodium bismuthate (NaBiO 3 ) assay. 7 A standard optical absorbance versus concentration curve was prepared with known concentrations of potassium permanganate (KMnO 4 ), which has distinctive pink color, using UV-Vis spectrophotometry at 578 nm. This standard curve was used to obtain the unknown concentration of permanganate (MnO …”

“…6 Graphene nanoparticles have been covalently functionalized with carboxylic acid, hydroxyl, 22 poly-L-lysine, 23 and non-covalently functionalized with synthetic polymer polyethylene glycol 6 or Pluronic F-127. 7 The maximum solubility reported for these functionalization approaches has been between 1 and 2 mg/mL. Recently, graphene nanoparticles have been covalently conjugated with the natural polymer dextran with a maximum water solubility of 1 mg/mL.…”

“…2 The two-dimensional carbon nanostructure graphene has attracted a great deal of attention for biomedical applications owing to its unique physicochemical properties. 6 are disc-shaped with diameters ∼20-40 nm and thickness ∼2-3 nm, paramagnetic, and their suspensions (0.1-1.0 mg/ mL concentrations) in biocompatible Pluronic ® F-127 (1 wt%; # P-3000MP, Life Technologies, Carlsbad, CA, USA) solutions at clinically relevant magnetic fields (eg, 1.5 Tesla) show an order of magnitude or greater r 1 relaxivity 7 (relaxivity r 1 or r 2 is a measure of the efficacy of an MRI CA, and is defined as the change in relaxation rate [inverse of T 1 8 The high relaxivity may allow the development of MRI CAs that show the same clinical MRI performance at substantially lower dosages, and could also allow their development for advanced applications such as MRI CAs for extended-residence-intravascular, tissue (organ)-specific, and molecular imaging. However, to translate this promising MRI CA into the clinic, the hydrophobic graphene nanoplatelets need to be water solubilized at much higher concentrations (in the range of tens of mg/mL) with suitable biocompatible moieties, and their stability needs to be ensured at these high concentrations in biological media or blood.…”