Nuclear spin relaxation in aqueous paramagnetic ion solutions.

A Brownian shell model describing the random rotational motion of a spherical shell of uniform particle density is presented and validated by molecular dynamics simulations. The model is applied to proton spin rotation in aqueous paramagnetic ion complexes to yield an expression for the Larmor-frequency-dependent nuclear magnetic resonance spin-lattice relaxation rate T_{1}^{-1}(ω) describing the dipolar coupling of the nuclear spin of the proton with the electronic spin of the ion. The Brownian shell model provides a significant enhancement to existing particle-particle dipolar models without added complexity, allowing fits to experimental T_{1}^{-1}(ω) dispersion curves without arbitrary scaling parameters. The model is successfully applied to measurements of T_{1}^{-1}(ω) from aqueous manganese(II), iron(III), and copper(II) systems where the scalar coupling contribution is known to be small. Appropriate combinations of Brownian shell and translational diffusion models, representing the inner and outer sphere relaxation contributions, respectively, are shown to provide excellent fits. Quantitative fits are obtained to the full dispersion curve of each aquoion with just five fit parameters, with the distance and time parameters each taking a physically justifiable numerical value.

Formation of hydrated PEG layers on magnetic iron oxide nanoflowers shows internal magnetisation dynamics and generates high in-vivo efficacy for MRI and magnetic hyperthermia.

Multicore magnetic iron oxide nanoparticles, nanoflowers (NFs), have potential biomedical applications as efficient mediators for AC-magnetic field hyperthermia and as contrast agents for magnetic resonance imaging due to their strong magnetic responses arising from complex internal magnetic ordering. To realise these applications amenable surface chemistry must be engineered that maintain particle dispersion. Here a catechol-derived grafting approach is described to strongly bind polyethylene glycol (PEG) to NFs and provide stable hydrogen-bonded hydrated layers that ensure good long-term colloidal stability in buffers and media even at clinical MRI field strength and high concentration. The approach enables the first comprehensive study into the MRI (relaxivity) and hyperthermic (SAR) efficiencies of fully dispersed NFs. The predominant role of internal magnetisation dynamics in providing high relaxivity and SAR is confirmed, and it is shown that these properties are unaffected by PEG molecular weight or corona formation in biological environments. This result is in contrast to traditional single core nanoparticles which have significantly reduced SAR and relaxivity upon PEGylation and on corona formation, attributed to reduced Brownian contributions and weaker NP solvent interactions. The PEGylated NF suspensions described here exhibit usable blood circulation times and promising retention of relaxivity in-vivo due to the strongly anchored PEG layer. This approach to biomaterials design addresses the challenge of maintaining magnetic efficiency of magnetic nanoparticles in-vivo for applications as theragnostic agents. STATEMENT OF SIGNIFICANCE: Application of multicore magnetic iron-oxide nanoflowers (NFs) as efficient mediators for AC-field hyperthermia and as contrast agents for MR imaging has been limited by lack of colloidal stability in complex media and biosystems. The optimized materials design presented is shown to reproducibly provide PEG grafted NF suspensions of exceptional colloidal stability in buffers and complex media, with significant hyperthermic and MRI utility which is unaffected by PEG length, anchoring group or bio-molecular adsorption. Deposition in the selected pancreatic tumour model mirrors liposomal formulations providing a quantifiable probe of tissue-level liposome deposition and relaxivity is retained in the tumour microenvironment. Hence the biomaterials design addresses the longstanding challenges of maintaining the in vivo magnetic efficiency of nanoparticles as theragnostic agents.

Correlating Magnetic Hyperthermia and Magnetic Resonance Imaging Contrast Performance of Cubic Iron Oxide Nanoparticles with Crystal Structural Integrity.

Magnetic iron oxide nanoparticles have multiple biomedical applications in AC-field hyperthermia and magnetic resonance imaging (MRI) contrast enhancement. Here, two cubic particle suspensions are analyzed in detail, one suspension displayed strong magnetic heating and MRI contrast efficacies, while the other responded weakly. This is despite them having almost identical size, morphology, and colloidal dispersion. Aberration-corrected scanning transmission electron microscopy, electron energy loss spectroscopy, and high-resolution transmission electron microscopy analysis confirmed that the spinel phase Fe3O4 was present in both samples and identified prominent crystal lattice defects for the weakly responding one. These are interpreted as frustrating the orientation of the moment within the cubic crystals. The relationship between crystal integrity and the moment magnitude and dynamics is elucidated for the case of fully dispersed single nanocubes, and its connection with the emergent hyperthermia and MRI contrast responses is established.

Graphene oxide modulates inter-particle interactions in 3D printable soft nanocomposite hydrogels restoring magnetic hyperthermia responses.

Hydrogels loaded with magnetic iron oxide nanoparticles that can be patterned and which controllably induce hyperthermic responses on AC-field stimulation are of interest as functional components of next-generation biomaterials. Formation of nanocomposite hydrogels is known to eliminate any Brownian contribution to hyperthermic response (reducing stimulated heating) while the Néel contribution can also be suppressed by inter-particle dipolar interactions arising from aggregation induced before or during gelation. We describe the ability of graphene oxide (GO) flakes to restore the hyperthermic efficiency of soft printable hydrogels formed using Pluronics F127 and PEGylated magnetic nanoflowers. Here, by varying the amount of GO in mixed nanocomposite suspensions and gels, we demonstrate GO-content dependent recovery of hyperthemic response in gels. This is due to progressively reduced inter-nanoflower interactions mediated by GO, which largely restore the dispersed-state Néel contribution to heating. We suggest that preferential association of GO with the hydrophobic F127 blocks increases the preponderance of cohesive interactions between the hydrophilic blocks and the PEGylated nanoflowers, promoting dispersion of the latter. Finally we demonstrate extrusion-based 3D printing with excellent print fidelity of the magnetically-responsive nanocomposites, for which the inclusion of GO provides significant improvement in the spatially-localized open-coil heating response, rendering the prints viable components for future cell stimulation and delivery applications.

Enhanced Stability and Emission Properties of Perylene Dyes by Surface Tethering: Preparation of Fluorescent Ru Nanoparticle Suspensions by Alkyne Linker Chemistry.

Spherical ruthenium nanoparticles (NPs) with a narrow size distribution were synthesised in ethanol by a facile low-temperature solvothermal process without the assistance of templates, structure-directing agents or post annealing/reduction treatments. Surface passivation with a fluorescent perylene dye (EP), and with silane ligands (ETMS), both initially bearing alkyne groups and subsequently forming vinylidene linkages, provided stable suspensions of the marginally soluble free EP. Quantitative analysis of the suspension gave an estimated EP surface coverage of 15 %, corresponding to an EP/ETMS mole ratio of ≈1:6. Photophysical evaluation of the bound and free dye revealed similar absorption bands and extinction coefficients and improved properties for the bound state, including enhanced fluorescence in the visible range for the bound dye, an extended absorption range into the near-UV providing strong emission in the visible, and significantly improved photostability. The physical basis of the enhanced photophysical properties, potential routes to further improvements and the implications for applications are discussed.

Spatiotemporally Resolved Heat Dissipation in 3D Patterned Magnetically Responsive Hydrogels.

Multifunctional nanocomposites that exhibit well-defined physical properties and encode spatiotemporally controlled responses are emerging as components for advanced responsive systems, for example, in soft robotics or drug delivery. Here an example of such a system, based on simple magnetic hydrogels composed of iron oxide magnetic nanoflowers and Pluronic F127 that generates heat upon alternating magnetic field irradiation is described. Rules for heat-induction in bulk hydrogels and the heat-dependence on particle concentration, gel volume, and gel exposed surface area are established, and the dependence on external environmental conditions in "closed" as compared to "open" (cell culture) system, with controllable heat jumps, of ∆T 0-12°C, achieved within ≤10 min and maintained described. Furthermore the use of extrusion-based 3D printing for manipulating the spatial distribution of heat in well-defined printed features with spatial resolution <150 µm, sufficiently fine to be of relevance to tissue engineering, is presented. Finally, localized heat induction in printed magnetic hydrogels is demonstrated through spatiotemporally-controlled release of molecules (in this case the dye methylene blue). The study establishes hitherto unobserved control over combined spatial and temporal induction of heat, the applications of which in developing responsive scaffold remodeling and cargo release for applications in regenerative medicine are discussed.

Template-Assisted Synthesis of Luminescent Carbon Nanofibers from Beverage-Related Precursors by Microwave Heating.

Luminescent carbon nanomaterials are important materials for sensing, imaging, and display technologies. This work describes the use of microwave heating for the template-assisted preparation of luminescent carbon nanofibers (CNFs) from the reaction of a range of beverage-related precursors with the nitrogen-rich polyethyleneimine. Highly luminescent robust carbon fibers that were 10 to 30 m in length and had a diameter of 200 nm were obtained under moderate conditions of temperature (250-260 °C) and a short reaction time (6 min). The high aspect ratio fibers showed wavelength-dependent emission that can be readily imaged using epifluorescence. The development of these multi-emissive one-dimensional (1D) carbon nanomaterials offers potential for a range of applications.