Carla J. Meledandri

Linear assemblies of magnetic nanoparticles as MRI contrast agents

Using a one-step procedure we have prepared magnetic fluids comprising of polyelectrolyte stabilized magnetite nanoparticles. These nanocomposites are comprised of linear, chain-like assemblies of magnetic nanoparticles, which can be aligned in parallel arrays by an external magnetic field. We have shown the potential use of these materials as contrast agents by measuring their MR response in live rats. The new magnetic fluids have demonstrated good biocompatibility and potential for in vivo MRI diagnostics.

Hierarchical gold-decorated magnetic nanoparticle clusters with controlled size.

We present a new route to stable magnetic-plasmonic nanocomposite materials with exceptional control over composite size and very high monodispersity. The method involves the assembly of magnetic iron oxide nanoparticles, of any size in the superparamagnetic size range, whose steric repulsion is gradually reduced by competitive stabilizer desorption arising from the presence of a tertiary silica phase. Subsequent addition of gold nanoparticles results in hierarchical assemblies in the form of gold-decorated magnetic nanoparticle clusters, in a range of possible sizes from 20 to 150 nm, selected by the timing of the addition. This approach adds plasmonic and chemical functionality to the magnetic clusters and improves the physical robustness and processability of the suspensions. Most critically, detailed NMR relaxation analysis demonstrates that the effect of the gold NPs on the interaction between bulk solvent and the magnetic moments of the cluster is minimal and that the clusters remain superparamagnetic in nature. These advantages enhance the potential of the materials as size-selected contrast agents for magnetic resonance imaging. The possibility of generalizing the approach for the production of hierarchical assemblies of variable composition is also demonstrated.

Nonaqueous Magnetic Nanoparticle Suspensions with Controlled Particle Size and Nuclear Magnetic Resonance Properties

We report the preparation of monodisperse maghemite (gamma-Fe2O3) nanoparticle suspensions in heptane, by thermal decomposition of iron(III) acetylacetonate in the presence of oleic acid and oleylamine surfactants. By varying the surfactant/Fe precursor mole ratio during synthesis, control was exerted both over the nanocrystal core size, in the range from 3 to 6 nm, and over the magnetic properties of the resulting nanoparticle dispersions. We report field-cycling 1H NMR relaxation analysis of the superparamagnetic relaxation rate enhancement of nonaqueous suspensions for the first time. This approach permits measurement of the relaxivity and provides information on the saturation magnetization and magnetic anisotropy energy of the suspended particles. The saturation magnetization was found to be in the expected range for maghemite particles of this size. The anisotropy energy was found to increase significantly with decreasing particle size, which we attribute to increased shape anisotropy. This study can be used as a guide for the synthesis of maghemite nanoparticles with selected magnetic properties for a given application.

Size-controlled magnetoliposomes with tunable magnetic resonance relaxation enhancements

Stable aqueous suspensions of phospholipid-coated superparamagnetic Fe3O4 nanoparticles, or magnetoliposomes (MLs), were prepared and were separated by magnetic chromatography into size monodisperse fractions over a broad size range (50–130 nm). This development facilitated the first study of the size dependence of the MRI relaxation enhancements (relaxivity) of the ML suspensions. The iron oxide surface was stabilised by a primary layer of phosphatidylglycerol, but a range of lipids could be used to complete the bilayer, ensuring water dispersibility and control of ML surface properties. This work establishes for the first time that the outer lipid headgroup has a strong influence on the water relaxation time. Thus our approach provides multiple means to tailor both the biodistribution and the relaxivity of ML suspensions for biomedical applications as contrast agents for MRI, or as magnetically actuated delivery vehicles.

Low field magnetic resonance techniques in the development of nanomaterials for biomedical applications

In recent years there has been rapid progress in the development of nanomaterials, and in particular magnetic nanomaterials, for magnetic resonance imaging and other biomedical applications. Using selected highlights from recent literature we describe the magnetic resonance methods that are used to measure the effects of agents on image contrast. We also show how these methods offer new insight into magnetic order in the colloidal state, a critical factor for all biomedical applications.

NMR Relaxation of Water in Nanostructures: Analysis of Ferromagnetic Cobalt–Ferrite Polyelectrolyte Nanocomposites

Polyelectrolyte-stabilised cobalt ferrite magnetic fluids demonstrate high relaxivity values at low fields. The magnetic suspensions are composed of compact metal oxide nanocomposites arranged in micelle-like structures which demonstrate an inverse correlation between relaxivity and hydrodynamic diameter (see graph). They can be aligned into linear arrays using an external magnet.

Temperature and Size-Dependence of Membrane Molecular Dynamics in Unilamellar Vesicles by Fast Field-Cycling NMR Relaxometry

New methods to study dynamics in lipid bilayers are of interest particularly where they may bridge the gap between conventional experimental techniques and molecular dynamics simulations. Fast field cycling nuclear magnetic resonance relaxometry can provide valuable information as it is sensitive to dynamic processes that occur over a broad time scale. By analysis of data recorded for large unilamellar liposomes composed of 1,2-dimyristoyl-sn-glycero-3-posphocholine (DMPC) or 1,2-dioleoyl-sn-glycero-3-posphocholine (DOPC) at different temperatures and sizes, we validate an evidence-based approach to studying dynamics by relaxometry. Specifically, the number and form of the spectral density contributions from a range of dynamic processes are determined. This success of the approach strongly suggests its general applicability for the study of dynamics in membranes of more complex composition and for parameterizing molecular dynamics simulations.

Interpretation of Molecular Dynamics on Different Time Scales in Unilamellar Vesicles Using Field-Cycling NMR Relaxometry

Fast field-cycling (FFC) and rotating-frame nuclear magnetic resonance relaxometry were used to study molecular and collective dynamics in unilamellar liposome systems. Relaxation data for liposomes of diameter about 100 nm composed of 1,2-dimyristoyl-sn-glycero-3-posphocholine (DMPC) or 1,2-dioleoyl-sn-glycero-3-posphocholine (DOPC) were obtained. The Larmor frequency dependence of the spin-lattice relaxation rates was interpreted in terms of clearly defined relaxation mechanisms associated with the underlying molecular dynamics. The physical parameters obtained from the analysis are consistent with values available in the literature obtained from a range of experimental techniques. This work establishes the potential of our approach to study dynamics in liposomal samples of more complex lipid composition.

Insights into the Partitioning Behavior of Secondary Surfactants in a Microemulsion-Based Synthesis of Metal Nanoparticles: A DLS and 2D NMR Spectroscopic Investigation

Diffusion-ordered NMR spectroscopy (DOSY) and nuclear Overhauser effect spectroscopy (NOESY) have been used to explore the diffusion and partitioning behavior of secondary surfactants added to suspensions of reverse micelles (RMs) containing either silver or gold nanoparticles (NPs), with an aim of advancing our understanding of the mechanism of metal NP extraction and/or surface functionalization with specific capping agents as performed during a microemulsion-based synthesis. We have coupled these NMR techniques with corresponding dynamic light scattering (DLS) measurements of RMs, with and without encapsulated metal NPs, upon addition of secondary surfactants. Using oleylamine (OAm), oleic acid (OA), dodecylamine (DDAm), and dodecanethiol (DDT), we show that all four secondary surfactants can rapidly diffuse into/out of the RM environment with their head groups in close proximity to the RM interior and encapsulated water molecules; however, surfactant molecules containing a terminal -NH2 or -COOH group undergo a persistent association with the molecules of the RMs, thus solubilizing and partially sequestering a portion of the total concentration of these secondary agents within the RM interface for a lengthened period of time (in relation to the time frame of the DOSY experiments) and slowing their rate of exchange with freely diffusing molecules in the bulk solvent. The extraction of Ag or Au NPs from RMs into organic phase was determined to be critically dependent on the type and concentration of secondary surfactant added to the system, with DDT proving to be most efficient for the extraction of Ag NPs, while OA was shown to be most efficient for Au NPs. Consideration of the results obtained from this particular combination of techniques has provided new knowledge with respect to dynamic metal NP-containing microemulsion systems.

The effect of cholesterol on membrane dynamics on different timescales in lipid bilayers from fast field-cycling NMR relaxometry studies of unilamellar vesicles.

The general applicability of fast field-cycling nuclear magnetic resonance relaxometry in the study of dynamics in lipid bilayers is demonstrated through analysis of binary unilamellar liposomes composed of 1,2-dioleoyl-sn-glycero-3-posphocholine (DOPC) and cholesterol. We extend an evidence-based method to simulating the NMR relaxation response, previously validated for single-component membranes, to evaluate the effect of the sterol molecule on local ordering and dynamics over multiple timescales. The relaxometric results are found to be most consistent with the partitioning of the lipid molecules into affected and unaffected portions, rather than a single averaged phase. Our analysis suggests that up to 25 mol%, each cholesterol molecule orders three DOPC molecules, providing experimental backup to the findings of many molecular dynamics studies. A methodology is established for studying dynamics on multiple timescales in unilamellar membranes of more complex compositions.