Magnetic resonance imaging (MRI) is a powerful non-invasive technique which becomes considerably more potent when contrast agents are introduced. Magnetic iron oxide nanoparticles have potential in biomedicine and have seen application as negative MRI contrast agents clinically, though their popularity has plummeted recently due to their low efficacy and safety concerns, including haemagglutination. There is therefore a real need for new CAs with excellent MRI contrast capabilities and good biocompatibility. Herein, we seek to explore the effect of a clinically-approved templating agent on protic relaxation behaviour – assessing the contrast agent behaviour of both reversible and permanent 1-D arrays of magnetic nanoparticles.
An in situ procedure is used to prepare colloidal magnetite nanoparticles, exploiting the clinically approved anti-coagulant, heparin, as a templating stabiliser. This preparative procedure provides control over vital interparticle interactions in ferrite nanocomposites, yielding stable aqueous colloids with exceptionally strong MRI contrast capabilities, particularly at low fields (r1 values of 37.2 mM-1s-1 and r2 values of 264.9 mM-1s-1 at 13.2 MHz), which outperform the current clinical standards. Relaxometric investigations using nuclear magnetic resonance dispersion (NMRD) techniques demonstrate that this behaviour is due to interparticle interactions, thanks to the templating effect of heparin, resulting in strong magnetic anisotropic behaviour. The stable colloidal nanoparticles have also been shown to prevent protein-adsorption triggered thrombosis, which causes unexpected (and potentially fatal) problems in the clinic. These species therefore show strong potential for in vivo MRI diagnostics.
The vital importance of shape anisotropy on resulting MR contrast has been further investigated through the production of permanent 1-D magnetic nanowires, using a novel magnetically-driven nanoparticle assembly preparative technique. These 1-D nanowires boast excellent relaxivity values (r2=278 mM-1s-1 at 13.1 MHz and r2/r1=16.7), showing strong potential for next-generation negative MRI contrast agents.