Chelating oleyl-EDTA amphiphiles: self-assembly, colloidal particles, complexation with paramagnetic metal ions and promise as magnetic resonance imaging contrast agents

Abstract

Chelating amphiphiles with N, N′-ethylene diamine tetraacetic acid (EDTA) conjugated via an ester bond to one or two oleyl chain/s (EDTA-MO and EDTA-BO) have been found to be capable of chelating a variety of metal ions including paramagnetic metal ions such as Manganese (Mn) and Gadolinium (Gd). Thermal behavior and stability were investigated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). X-ray diffraction (XRD), polarizing optical microscopy (POM) and synchrotron small and wide angle X-ray scattering (SWAXS) were used to examine the neat and lyotropic liquid crystalline phases of these amphiphiles. Aqueous colloidal dispersions of EDTA-MO and EDTA-BO and their paramagnetic metal ion chelates were examined by synchrotron SAXS, cryogenic transmission electron microscopy (cryo-TEM) and light scattering. The complexed colloidal particles were evaluated as contrast enhancement agents (CEAs) for magnetic resonance imaging (MRI) using low field NMR. Neat EDTA-MO and EDTA-BO displayed lamellar crystalline structures at room temperature. EDTA-MO in excess water or sodium acetate solution exhibited a lamellar liquid crystalline phase (L_α) across a broad range of temperatures, whereas EDTA-BO displayed a very rich polymorphism from lamellar to inverse cubic and inverse hexagonal phases depending on the ionic strength of the aqueous solution and temperature employed. Dispersion of the bulk lyotropic liquid crystalline phases of both amphiphiles in aqueous Na-acetate solution yielded stable and predominantly liposomal particles at room temperature. Complexation of an EDTA-MO colloidal dispersion with Mn(II) or Gd(III) ions resulted in liposomal particles with significantly enhanced relaxivity values when compared with their low molecular weight counterparts Mn-EDTA and Gd-EDTA. In contrast, complexation of the EDTA-BO colloidal dispersion with Mn(II) altered the liposomal structure to highly ordered cylindrical multi-wall lipid nanotubes (MWLNTs). Again the relaxivity values were enhanced significantly in comparison with the Mn-EDTA analogue. In particular, the transverse relaxivity value of these complexed colloidal particles was enhanced significantly, which suggests that these MWLNTs have potential for use as both T₁ and T₂-weighted contrast agents.