Eoin K. Fox

Water-Soluble Superparamagnetic Magnetite Nanoparticles with Biocompatible Coating for Enhanced Magnetic Resonance Imaging

Ultrasmall superparamagnetic Fe(3)O(4) nanoparticles (USIRONs) were synthesized by a novel, easily scalable chemical reduction of colloidal iron hydroxide under hydrothermal conditions. The average crystallite size (5.1 ± 0.5 nm) and good crystallinity of the samples were supported by HR-TEM analysis and the saturation magnetization value (47 emu g(-1)). Vitamin C, used as a chemical reducing agent, also served as a capping agent in the oxidized form (dehydroascorbic acid, DHAA) to impart nanoparticles with exceptional solubility and stability in water, PBS buffer, and cell culture medium. Detailed physicochemical analysis of the USIRON suspensions provided insight into the magnetic ordering phenomena within the colloid, arising from the formation of uniform clusters displaying a hydrodynamic size of 41 nm. Phantom experiments on the contrast agent (clinical 3 T MRI scanner) revealed an enhanced r(2)/r(1) ratio of 36.4 (r(1)= 5 s(-1) mM(-1) and r(2)= 182 s(-1) mM(-1)) when compared to the clinically approved agents. The potential of the DHAA-Fe(3)O(4) nanoparticles as negative contrast agents for MRI with optimal hydrodynamic size for extended blood circulation times was confirmed by strong contrast observed in T(2)- and T(2)*-weighted images. The cell tests performed with primary human immune-competent cells confirmed the excellent biocompatibility of USIRONs.

pH control of the electrostatic binding of gold and iron oxide nanoparticles to tobacco mosaic virus.

We report the binding of nanoparticles (NPs) to wild type (unmodified) tobacco mosaic virus (TMV). The viruses are simply mixed with citrate-coated, negatively charged gold and iron oxide nanoparticles (IONPs) in acidic solution. This results in TMV decorated along its whole length by the respective particles. Such a decoration usually requires chemical modification or mutation of TMV (e.g., cysteine residues), but here we simply reduce TMVs natural negative charge by protonation. The particles are protonated to a much smaller extent. This charge-based mechanism does not operate for neutral particles.

Gadolinium-loaded polychelating amphiphilic polymer as an enhanced MRI contrast agent for human multiple myeloma and non Hodgkin's lymphoma (human Burkitt's lymphoma)

Liposomes, loaded with gadolinium (Gd) ions using different membrane-incorporated chelating lipids and functionalized with monoclonal anti-CD138 (syndecan-1) antibody were prepared. Nuclear Magnetic Resonance Dispersion (NMRD) analysis showed that use of the polychelating amphiphilic polymer (PAP) increases both the Gd content and the spin–lattice relaxivity of the Gd-loaded-PAP–liposomes as compared to Gd–DTPA–BSA equivalents. The potential application of contrast syndecan-1– and Rituximab–liposomes, for application as a novel minimally invasive diagnostic agent for multiple myeloma and non Hodgkins lymphoma was investigated.

Monodisperse magnetic nanoparticle assemblies prepared at scale by competitive stabiliser desorption

We report a scalable and reproducible method to assemble magnetic nanoparticle clusters from oleic acid stabilised iron oxide nanoparticles. By controlling the surface coverage of oleic acid on the nanoparticle surface we have achieved controlled nanoparticle assembly following exposure of the suspension to a substrate layer of cyanopropyl-modified silica which competes for the ligand. The clusters can be formed reproducibly and their final size can be selected over a range covering almost two orders of magnitude. Most unusually, the relative monodispersity of the cluster suspension is improved compared to the starting nanoparticle suspension, and the yield is close to 100%. Interestingly, we find that the kinetics of assembly is not altered by scaling up, which is surprising for a complex process involving molecular transport. Kinetic studies provided mechanistic insight into the process, and suggested general requirements for controlled assembly of other nanoparticle types.

Optimisation of a novel glass-alginate hydrogel for the treatment of intracranial aneurysms

The current gold standard for aneurysm treatment is endovascular coiling. However, recurrence is observed in over 20% of cases. A novel hydrogel has been developed to treat aneurysms. This hydrogel is composed of a polymeric alginate, a novel ion releasing glass and glucono-delta-lactone. This is an internally setting alginate hydrogel, wherein the setting rate can be controlled by both the glass and the alginate chemistry. The aim of this work is to examine the effect of each component of the hydrogel and optimise the composition of the hydrogel, specifically the alginate molecular weight, M/G ratio and concentration. The effects of gamma sterilisation will also be examined. The results show that alginate concentration, chemical composition and molecular weight affect the compressive strength, working time, hardening time and deliverability of the hydrogel. Gamma irradiation of the alginate reduces the molecular weight, which has a negative effect on the usability of this hydrogel.

Glyco-copolypeptide grafted magnetic nanoparticles: the interplay between particle dispersion and RNA loading

Lysine-glyco-copolypeptide grafted superparamagnetic iron oxide nanoparticles were prepared through N-carboxyanhydride (NCA) copolymerization. Statistical and block copolymer arrangements were obtained while keeping the overall composition constant. Both type of nanoparticles are fully water dispersible, which is key for T1-weighted magnetic resonance imaging (MRI) applications. A synergistic effect between siRNA loading and imaging properties was observed in the statistical copolymer arrangement allowed a significantly higher loading while retaining full particle dispersion, as required for T1-weighting.

Surface modification of a novel glass to optimise strength and deliverability of an injectable alginate composite

It is estimated that 1–6% of the adult population have an intracranial aneurysm. Aneurysm coiling is the current preferred treatment method; however, over 20% of coiled aneurysms recur. A novel glass–alginate composite hydrogel has been developed to treat aneurysms, which is designed to completely fill the aneurysm space and prevent aneurysm recurrence. This hydrogel is composed of a polymeric alginate, a novel bioactive glass and glucono-delta-lactone. This novel injectable hydrogel exhibits characteristics suitable for the treatment of cerebral aneurysms. However, poor hydrophilicity of the glass phase results in inhomogeneity and agglomerate formation within the composite, resulting in suboptimal deliverability and strength. This study examines the effect of surface modification of the glass particles using an acid washing technique, designed to increase glass surface hydrophilicity resulting in a homogeneous sample. This study found that acid washing of the glass not only decreased agglomeration and inhomogeneity but also lengthened working times and increased strength of the resultant hydrogel. This lengthened working time, allowed for an increased glass content and, as a result, further increased compressive strength and radiopacity of the resultant hydrogel. Glass particle size analysis revealed that the relative quantity of fine particles was reduced. Surface analysis of the glass particles revealed an increase in hydrophilic silanol groups and increased surface network connectivity. These factors, combined with a decreased surface calcium and an increased surface gallium content, are postulated as the likely reasons for the observed increased strength, working time and hardening time.

Size-Controlled Nanoparticle Clusters of Narrow Size-Polydispersity Formed Using Multiple Particle Types Through Competitive Stabilizer Desorption to a Liquid-Liquid Interface

A novel colloidal approach is presented for preparing fully dispersed nanoparticle (NP) assemblies (clusters) of narrow size-polydispersity over a wide range of sizes through irreversible depletion of stabilizing ligands onto a liquid-liquid interface. Unusually, the relative monodispersity of the assemblies continuously improves throughout the process. A detailed kinetics study into the assembly of iron oxide NP clusters shows that the assembly rate decreases with NP concentration, pinpointing the role of the interface in size focusing. A new protocol for identifying initial conditions that enable controlled assembly is described, which allows extension of the approach to multiple NP types, opening up a general route to colloidally processed materials. The process uses cheap materials, it is reproducible, robust, and scaleable, and it allows for selection of both particle and cluster size. In the case of assemblies of magnetic iron oxide NPs, these advantages enable tuning of the magnetic properties of the assemblies for applications such as magnetically targetable MRI-trackable agents in biomedicine.