Amalgamation of complex iron(III) ions and iron nanoclusters with MWCNTs as a route to potential T2 MRI contrast agents

Abstract

Iron-filled multiwall carbon nanotubes (Fe@MWCNTs) were functionalized toward a variety of potential magnetic resonance imaging contrast agents. Oxidized Fe@MWNCTs were covered with PEG5000 via direct esterification or using acyl chloride derivatives. Alternatively, the latter were functionalized with an aminophenol ligand (Fe@O-MWCNT-L). Moreover, pristine Fe@MWCNTs were functionalized with N -phenylaziridine groups (Fe@f-MWCNT) via [2+1] cycloaddition of nitrene. All of these chemically modified nanotubes served as a vehicle for anchoring Fe 3+ ions. The new hybrids – Fe(III)/Fe@(f-/O-)MWCNTs – containing 6%–14% of the “tethered” Fe 3+ ions were studied in terms of the acceleration of relaxation of water protons in nuclear magnetic resonance. The highest transverse relaxivity r 2 =63.9±0.9 mL mg −1 s −1 was recorded for Fe(III)/Fe@O-MWCNT-L, while for Fe(III)/Fe@f-MWCNT, with r 2 =57.9±2.9 mL mg −1 s −1 , the highest impact of the anchored Fe(III) ions was observed. The T 1 / T 2 ratio of 30–100 found for all of the nanotube hybrids presented in this work is a very important factor for their potential application as T 2 contrast agents. Increased stability of the hybrids was confirmed by ultraviolet–visible spectrophotometry.

<p>Oxygen Functional Groups on MWCNT Surface as Critical Factor Boosting T2 Relaxation Rate of Water Protons: Towards Improved CNT-Based Contrast Agents</p>

“…Acceleration of the relaxation rate in relaxometric measurements was significant for T 2 , while T 1 relaxation was independent of the concentration of MWCNTs which was also observed in our previous study. 16 It is expected that a promising T 2 CA should show considerably reduced T 2 relaxation time increasing darkness in T 2 -weighted images. The MWCNT O samples yielded darker images compared with the MWCNT N samples in phantom MRI studies as shown in Figure 5C.…”

“…Currently, two major routes toward MWCNT-CAs have been developed: MWCNTs are decorated with magnetic nanoparticles or magnetic nanoparticles are encapsulated inside MWCNTs. Depending on the type of magnetic nanoparticles MWCNT-CAs may act as T 1 CAs, when Gd 3+ ions 11 or Gd-containing nanoparticles 12 are used, while α-Fe, [13][14][15][16] Fe 3+ ions, 15,16 and SPIONs [17][18][19] typically lead to T 2 CAs.…”

“…13 Here, the main route of MWCNT functionalization consists of surface oxidation by wet techniques which themselves produce nanohybrids that can form stable aqueous dispersions. 15,16,20 Moreover, carboxylic groups produced in the process are used as covalent or non-covalent anchors for biocompatible polymers, eg, polyethylene glycol (PEG), 16,21 polystyrene sulfonate (PSS), or polyethylenimine (PEI). 22 Relaxivities r 2 reported for these Fe@MWCNT CAs range from 22 mM −1 s −1 to 564 mM −1 s −1 (Table 1).…”

“…Decoration of MWCNTs with magnetic species is a step-by-step process involving functionalization of the carbon surface, which yields linkers between MWCNT and magnetic nanoparticles – typically Gd 3+ ions 11 or SPIONs. 18 MWCNT surface can be oxidized by HNO 3 :H 2 SO 4 mixture to generate carboxylic moieties on the MWCNT surface which act as ligands itself 15 or as an anchor for ligands such as aminophenol compounds for Fe 3+ ions coordination 16 or lactose-glycine adducts which form stable complexes with SPIO. 18 On the other hand, ligands for Gd 3+ can be also introduced next to the already existing carboxylic groups by follow-up reactions of amino groups introduced through 1,3-dipolar cycloaddition.…”

“…22 Relaxivities r 2 reported for these Fe@MWCNT CAs range from 22 mM −1 s −1 to 564 mM −1 s −1 ( Table 1 ). 9 , 15 , 16 , 21 , 23 The broad scale of these r 2 -values arises from the fact that multiple Fe@MWCNTs properties have been reported to affect the T 2 relaxation rate, including their diameter, length, iron content, phase composition of the magnetic core, size of the iron core, and amount and type of functional groups on the surface 24 ( Table 1 ). Based on mainly ferromagnetic and paramagnetic behavior of iron particles inside Fe@MWCNTs, the mode of action as T 2 CAs can be compared with, eg, albumin coated ferromagnetic iron oxide nanoparticles where the magnetic core is also separated from water molecules by a large protein coating.…”