A Novel Device for the Quantification of Synovial Fluid Viscosity Via Magnetic Deflection.

Changes in synovial fluid viscosity may be used to detect joint disease; however, methods to evaluate these changes at the point-of-care are currently rudimentary. Previously, we demonstrated that magnetic particle translation through static synovial fluid could serve as a surrogate marker of synovial fluid mechanics. In this work, we examine the magnetic deflection of a stream of particles flowing through a stream of synovial fluid and relate this deflection to changes in fluid mechanics. First, a flow device was designed, where a stream of magnetic particles flows along with synovial fluid. As the particle stream approaches and passes a fixed permanent magnet, the particle stream deflects. Conceptually, as the synovial fluid viscosity decreases, the deflection of the particle stream should increase due to a decreased drag force opposing the force magnetization. To assess this concept, particle deflection was first measured in Newtonian glycerol solutions of known varying viscosity under different flow conditions. Next, the device was used to test bovine synovial fluid viscosity, which had been progressively degraded using ultrasonication. A strong correlation was observed between the deflection of the magnetic particles and the viscosity of the glycerol solutions (R2 = 0.987) and the amount of ultrasonic degradation of synovial fluid (R2 = 0.7045). In the future, the principle of particle deflection may be used to design point-of-care quantification of synovial fluid mechanics, as the assessment does not require particles to be separated from the fluid for quantification and could be conducted under simple flow conditions.

Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics.

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/ß-catenin signaling is linked to cancer. Therefore, technologies for local modulation and control of Wnt signaling targeted to specific sites of disease or degeneration have potential therapeutic value in the treatment of degenerative diseases. We reported a facile approach to locally activate the canonical Wnt signaling cascade using nanomagnetic actuation or ligand immobilized platforms. Using a human embryonic kidney (HEK293) Luc-TCF/LEF reporter cell line, we demonstrated that targeting the cell membrane Wnt receptor, Frizzled 2, with peptide-tagged magnetic nanoparticles (MNPs) triggered canonical Wnt signaling transduction when exposed to a high-gradient, time-varying magnetic field, and the induced TCF/LEF signal transduction was shown to be avidity-dependent. We also demonstrated that the peptide retained signaling activity after functionalization onto glass surfaces, providing a versatile platform for drug discovery or recreation of the cell niche. In conclusion, these results showed that peptide-mediated Wnt signaling kinetics depended not only on ligand concentration but also on the presentation method of the ligand, which may be further modulated by magnetic actuation. This has important implications when designing future therapeutic platforms involving Wnt mimetics.

Use of magnetic capture to identify elevated levels of CCL2 following intra-articular injection of monoiodoacetate in rats.

PURPOSE: Synovial fluid biomarkers help evaluate osteoarthritis (OA) development. Magnetic capture, our new magnetic nanoparticle-based technology, has proven to be effective for determining extracellular matrix fragment levels in two rat OA models. Here, the feasibility of magnetic capture for detecting monocyte chemoattractant protein-1 (MCP-1 or CCL2) is demonstrated after intra-articular injection of monoiodoacetate (MIA) in the rat knee. METHODS: Forty-eight male Lewis rats received a right hind limb, intra-articular injection of MIA (1 mg in 25 µl of saline) or 25 µl of saline. Magnetic capture and lavage were performed at 7 days after injection (n = 6 per treatment per procedure), with magnetic capture additionally performed at 14 and 28 days post-injection (n = 6 per treatment per time point). CCL2 was also assessed in serum. RESULTS: Serum CCL2 levels revealed no difference between MIA and saline animals (p = 0.0851). In contrast, magnetic capture and lavage detected a significant increase of CCL2 in the MIA-injected knee, with the MIA-injected knee having elevated CCL2 compared to contralateral and saline-injected knees (p = 0.00016 (contralateral) and p = 0.00016 (saline) for magnetic capture; p = 0.00023 (contralateral) and p = 0.00049 (saline) for lavage). CONCLUSIONS: Magnetic capture of CCL2 was successfully developed and applied to determine levels of CCL2 in a rat knee. Magnetic capture detected a statistically significant increase of CCL2 in MIA-injected knees compared to controls, and CCL2 levels stayed relatively stable from week 1 through week 4 post-MIA injection.

Evaluation of magnetic nanoparticles for magnetic fluid hyperthermia.

Background: Magnetic nanoparticles (MNPs) generate heat when exposed to an alternating magnetic field. Consequently, MNPs are used for magnetic fluid hyperthermia (MFH) for cancer treatment, and have been shown to increase the efficacy of chemotherapy and/or radiation treatment in clinical trials. A downfall of current MFH treatment is the inability to deliver sufficient heat to the tumor due to: insufficient amounts of MNPs, unequal distribution of MNPs throughout the tumor, or heat loss to the surrounding environment. Objective: In this study, the objective was to identify MNPs with high heating efficiencies quantified by their specific absorption rate (SAR). Methods: A panel of 31 commercially available MNPs were evaluated for SAR in two different AMFs. Additionally, particle properties including iron content, hydrodynamic diameter, core diameter, magnetic diameter, magnetically dead layer thickness, and saturation mass magnetization were investigated. Results: High SAR MNPs were identified. For SAR calculations, the initial slope, corrected slope, and Box-Lucas methods were used and validated using a graphical residual analysis, and the Box-Lucas method was shown to be the most accurate. Other particle properties were identified and examined for correlations with SAR values. Positive correlations of particle properties with SAR were found, including a strong correlation for the magnetically dead layer thickness. Conclusions: This work identified high SAR MNPs for hyperthermia, and provides insight into properties which correlate with SAR which will be valuable for synthesis of next-generation MNPs. SAR calculation methods must be standardized, and this work provides an in-depth analysis of common calculation methods.

Carbodiimide Conjugation of Latent Transforming Growth Factor ß1 to Superparamagnetic Iron Oxide Nanoparticles for Remote Activation.

Conjugation of latent growth factors to superparamagnetic iron oxide nanoparticles (SPIONs) is potentially useful for magnetically triggered release of bioactive macromolecules. Thus, the goal of this work was to trigger the release of active Transforming Growth-Factor Beta (TGF-ß) via magnetic hyperthermia by binding SPIONs to the latent form of TGF-ß, since heat has been shown to induce release of TGF-ß from the latent complex. Commercially available SPIONS with high specific absorption rates (SAR) were hydrolyzed in 70% ethanol to create surface carboxylic acid conjugation sites for carbodiimide chemistry. Fourier-Transform Infra-Red (FTIR) analysis verified the conversion of maleic anhydride to maleic acid. 1-Ethyl-2-(3-dimethyulaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS) were used to bind to the open conjugation sites of the SPION in order to graft latent TGF-ß onto the particles. The resulting conjugated particles were imaged with transmission electron microscopy (TEM), and the complexed particles were characterized by dynamic light scattering (DLS) and superconducting quantum interference device (SQUID) magnetometry. Enzyme-linked immunosorbent assay (ELISA) was used to assess the thermally triggered release of active TGF-ß from the latent complex, demonstrating that conjugation did not interfere with release. Results showed that latent TGF-ß was successfully conjugated to the iron oxide nanoparticles, and magnetically triggered release of active TGF-ß was achieved.

A coil system for real-time magnetic fluid hyperthermia microscopy studies.

PURPOSE: We describe the design and application of a new apparatus for applying Radiofrequency (RF) electromagnetic fields to cells in culture on a microscope stage. This new design enables real-time studies of the actuation of magnetic nanoparticles bound to membrane receptors or internalised within cells together with the study of magnetic fluid hyperthermia (MFH)-associated effects. MATERIALS AND METHODS: RF coils were fabricated and electromagnetic simulations were performed along with compatibility evaluations and calorimetric experiments using this apparatus at discreet frequencies between 100 kHz and 1 MHz. Cell killing via MFH was investigated in a neuroblastoma tumour cell line. RESULTS: Simulations and evaluations showed that the field intensity and homogeneity experienced by the cells within the chamber is best with a planar coil configuration. The incubation chamber was suitable for cell culture and the design was compatible with mountings on different makes of microscopes as it mimics a standard 96/24/6 tissue-culture well plate. Successful calorimetric and MFH cytotoxicity proof-of-principle experiments were performed and are presented. CONCLUSIONS: We conclude from these experiments that alternating magnetic field (AMF)-mediated activation and magnetic fluid hyperthermia (MFH) research will benefit from this RF coil that fits inside an incubation chamber, mounted onto a microscope. This new design could be used to assist real-time MFH studies in vitro.

DNA Targeting Sequence Improves Magnetic Nanoparticle-Based Plasmid DNA Transfection Efficiency in Model Neurons.

Efficient non-viral plasmid DNA transfection of most stem cells, progenitor cells and primary cell lines currently presents an obstacle for many applications within gene therapy research. From a standpoint of efficiency and cell viability, magnetic nanoparticle-based DNA transfection is a promising gene vectoring technique because it has demonstrated rapid and improved transfection outcomes when compared to alternative non-viral methods. Recently, our research group introduced oscillating magnet arrays that resulted in further improvements to this novel plasmid DNA (pDNA) vectoring technology. Continued improvements to nanomagnetic transfection techniques have focused primarily on magnetic nanoparticle (MNP) functionalization and transfection parameter optimization: cell confluence, growth media, serum starvation, magnet oscillation parameters, etc. Noting that none of these parameters can assist in the nuclear translocation of delivered pDNA following MNP-pDNA complex dissociation in the cell's cytoplasm, inclusion of a cassette feature for pDNA nuclear translocation is theoretically justified. In this study incorporation of a DNA targeting sequence (DTS) feature in the transfecting plasmid improved transfection efficiency in model neurons, presumably from increased nuclear translocation. This observation became most apparent when comparing the response of the dividing SH-SY5Y precursor cell to the non-dividing and differentiated SH-SY5Y neuroblastoma cells.

Evidence of redox-active iron formation following aggregation of ferrihydrite and the Alzheimer's disease peptide ß-amyloid.

Recent work has demonstrated increased levels of redox-active iron biominerals in Alzheimer's disease (AD) tissue. However, the origin, nature, and role of iron in AD pathology remains unclear. Using X-ray absorption, X-ray microspectroscopy, and electron microscopy techniques, we examined interactions between the AD peptide ß-amyloid (Aß) and ferrihydrite, which is the ferric form taken when iron is stored in humans. We report that Aß is capable of reducing ferrihydrite to a pure iron(II) mineral where antiferromagnetically ordered Fe(2+) cations occupy two nonequivalent crystal symmetry sites. Examination of these iron(II) phases following air exposure revealed a material consistent with the iron(II)-rich mineral magnetite. These results demonstrate the capability of Aß to induce the redox-active biominerals reported in AD tissue from natural iron precursors. Such interactions between Aß and ferrihydrite shed light upon the processes of AD pathogenesis, while providing potential targets for future therapies.

Control of smooth muscle α-actin (SMA) up-regulation in HBMSCs using remote magnetic particle mechano-activation.

Physical cues have the potential to guide stem cell fate by coupling a mechanical stimulus to biochemical signaling. We have postulated that mechanical stimulation could provide a control method for cell therapy applications. This study investigates the use of functionalized magnetic nanoparticles to promote hBMSC differentiation towards a smooth muscle cell lineage by direct mechanical stimulation of platelet-derived growth factor receptor α and ß (PDGFRα and ß) via exposure to time-varying magnetic fields. Cyclical magneto-mechanical stimulation of PDGFR α over a 3h period results in up-regulation of smooth muscle α-actin expression in both protein and mRNA level. PDGFRα phosphorylation is detected in response to stimulation and the mRNA up-regulation is abrogated by pretreatment of cells with a receptor inhibitor, AG1296 or the neutralization antibody. Our results demonstrate proof of concept for remote controlled, locally-delivered mechanically induced differentiation of hBMSCs which could have applications in regenerative medicine. FROM THE CLINICAL EDITOR: Using a cyclical magneto-mechanical stimulator, this team of investigators demonstrated successful differentiation induction of human bone marrow-derived stem cells toward smooth muscle protein expression, with potential future applications in regenerative medicine.

Magnetic fluid hyperthermia: advances, challenges, and opportunity.

Though the concepts of magnetic fluid hyperthermia (MFH) were originally proposed over 50 years ago, the technique has yet to be successfully translated into routine clinical application. Significant challenges must be addressed if the field is to progress and realise its potential as an option for treatment of diseases such as cancer. These challenges include determining the optimum fields and frequencies that maximise the effectiveness of MFH without significant detrimental off-target effects on healthy tissue, achieving sufficient concentrations of magnetic nanoparticles (MNPs) within the target tumour, and developing a better mechanistic understanding of MNP-mediated energy deposition and its effects on cells and tissue. On the other hand, emerging experimental evidence indicates that local thermal effects indeed occur in the vicinity of energy-dissipating MNPs. These findings point to the opportunity of engineering MNPs for the selective destruction of cells and/or intracellular structures without the need for a macroscopic tissue temperature rise, in what we here call magnetically mediated energy delivery (MagMED).

Receptor-targeted, magneto-mechanical stimulation of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors-platelet-derived growth factor receptor α (PDGFRα) and integrin ανß3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανß3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation.

Materials characterization of Feraheme/ferumoxytol and preliminary evaluation of its potential for magnetic fluid hyperthermia.

Feraheme, is a recently FDA-cleared superparamagnetic iron oxide nanoparticle (SPION)-based MRI contrast agent that is also employed in the treatment of iron deficiency anemia. Feraheme nanoparticles have a hydrodynamic diameter of 30 nm and consist of iron oxide crystallites complexed with a low molecular weight, semi-synthetic carbohydrate. These features are attractive for other potential biomedical applications such as magnetic fluid hyperthermia (MFH), since the carboxylated polymer coating affords functionalization of the particle surface and the size allows for accumulation in highly vascularized tumors via the enhanced permeability and retention effect. This work presents morphological and magnetic characterization of Feraheme by transmission electron microscopy (TEM), Energy dispersive X-ray spectroscopy (EDX), and superconducting quantum interference device (SQUID) magnetometry. Additionally, the results of an initial evaluation of the suitability of Feraheme for MFH applications are described, and the data indicate the particles possess promising properties for this application.

High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: quantitative imaging and correlation with iron.

We report R(2) and R(2) in human hippocampus from five unfixed post-mortem Alzheimer's disease (AD) and three age-matched control cases. Formalin-fixed tissues from opposing hemispheres in a matched AD and control were included for comparison. Imaging was performed in a 600MHz (14T) vertical bore magnet at MR microscopy resolution to obtain R(2) and R(2) (62 µm×62 µm in-plane, 80 µm slice thickness), and R(1) at 250 µm isotropic resolution. R(1), R(2) and R(2) maps were computed for individual slices in each case, and used to compare subfields between AD and controls. The magnitudes of R(2) and R(2) changed very little between AD and control, but their variances in the Cornu Ammonis and dentate gyrus were significantly higher in AD compared for controls (p<0.001). To investigate the relationship between tissue iron and MRI parameters, each tissue block was cryosectioned at 30 µm in the imaging plane, and iron distribution was mapped using synchrotron microfocus X-ray fluorescence spectroscopy. A positive correlation of R(2) and R(2)* with iron was demonstrated. While studies with fixed tissues are more straightforward to conduct, fixation can alter iron status in tissues, making measurement of unfixed tissue relevant. To our knowledge, these data represent an advance in quantitative imaging of hippocampal subfields in unfixed tissue, and the methods facilitate direct analysis of the relationship between MRI parameters and iron. The significantly increased variance in AD compared for controls warrants investigation at lower fields and in-vivo, to determine if this parameter is clinically relevant.

Novel magnetite-silica nanocomposite (Fe3O4-SBA-15) particles for DNA binding and gene delivery aided by a magnet array.

Novel magnetite-silica nanocomposite particles were prepared using SBA-15 nanoporous silica as template. Magnetite nanoparticles were impregnated into the nanopore array of the silica template through thermal decomposition of iron(III) acetylacetonate, Fe(AcAc)3 at 200 degrees C. These composite particles were characterized using TEM, XRD and SQUID magnetometry. The TEM images showed that the size of composite particles was around 500 nm and the particles retained the nanoporous array of SBA-15. The formation of magnetite nanoparticles was confirmed by the powder XRD study. These composite particles also exhibited ferrimagnetic properties. By coating with short chain polyethyleneimine (PEI), these particles are capable of binding DNA molecules for gene delivery and transfection. With an external magnetic field, the transfection efficiency was shown to have an increase of around 15%. The results indicated that these composite nanoparticles may be further developed as a new tool for nanomagnetic gene transfection.

Model of Magnetic Particle Capture Under Physiological Flow Rates for Cytokine Removal During Cardiopulmonary Bypass.

OBJECTIVE: The objective of this study is to design a physical model of a magnetic filtration system which can separate magnetic nanoparticle (MNP)-tagged cytokines from fluid at physiologically relevant flow rates employed during cardiopulmonary bypass (CPB) procedures. METHODS: The Navier-Stokes equations for the pressure driven flow in the chamber and the quasistatic stray magnetic field produced by an array of permanent magnets were solved using finite element analysis in COMSOL Multiphysics for 2D and 3D representations of the flow chamber. Parameters affecting the drag and magnetic forces including flow chamber dimensions, high gradient magnet array configurations, and particle properties, were changed and evaluated for their effect on MNP capture. RESULTS: Flow chamber dimensions which achieve appropriate flow conditions for CPB were identified, and magnetic force within the chamber decreased with increased chamber height. A magnetic "block" array produced the highest magnetic force within the chamber. Polymeric microparticles loaded with MNPs were shown to have increased particle capture with increased hydrodynamic diameter. CONCLUSION: The model achieved a predicted efficiency up to 100% capture in a single-pass of fluid flowing at 1.75 L/min. SIGNIFICANCE: This work is an important step in designing a magnetic flow chamber that can remove the magnetically tagged cytokines under high flow employed during CPB. Cytokines have been shown to stimulate the systemic inflammatory response (SIR) associated with CPB and are an established therapeutic target to mitigate the SIR. In the long term, this work aims to guide researchers in the more accurate design of magnetic separation systems.

Magnetically Responsive Polymeric Microparticles for the Triggered Delivery of a Complex Mixture of Human Placental Proteins.

Bone loss through traumatic injury is a significant clinical issue. Researchers have created many scaffold types to mimic an extracellular matrix to provide structural support for the formation of new bone, however functional regeneration of larger scaffolds has not been fully achieved. Newer scaffolds aim to deliver bioactive molecules to improve tissue regeneration. To achieve a more comprehensive regenerative response, a magnetically triggerable polymeric microparticle platform is developed for the on-demand release of a complex mixture of isolated human placental proteins. This system is composed of polycaprolactone (PCL) microparticles, encapsulating magnetic nanoparticles (MNPs), and placental proteins. When subjected to an alternating magnetic field (AMF), the MNPs heat and melt the PCL, enhancing the diffusion of proteins from microparticles. When the field is off, the PCL re-solidifies. This potentially allows for cyclic drug delivery. Here the design, synthesis, and proof-of-concept experiments for this system are reported. In addition, it is shown that the proteins retain function after being magnetically released. The ability to trigger the release of complex protein mixtures on-demand may provide a significant advantage with wounds where stagnation of healing processes can occur (e.g., large segmented bone defects).

Iron stored in ferritin is chemically reduced in the presence of aggregating Aß(1-42).

Atypical low-oxidation-state iron phases in Alzheimer's disease (AD) pathology are implicated in disease pathogenesis, as they may promote elevated redox activity and convey toxicity. However, the origin of low-oxidation-state iron and the pathways responsible for its formation and evolution remain unresolved. Here we investigate the interaction of the AD peptide ß-amyloid (Aß) with the iron storage protein ferritin, to establish whether interactions between these two species are a potential source of low-oxidation-state iron in AD. Using X-ray spectromicroscopy and electron microscopy we found that the co-aggregation of Aß and ferritin resulted in the conversion of ferritin's inert ferric core into more reactive low-oxidation-states. Such findings strongly implicate Aß in the altered iron handling and increased oxidative stress observed in AD pathogenesis. These amyloid-associated iron phases have biomarker potential to assist with disease diagnosis and staging, and may act as targets for therapies designed to lower oxidative stress in AD tissue.

Multifunctional nanoparticles for intracellular drug delivery and photoacoustic imaging of mesenchymal stem cells.

Strategies that control the differentiation of mesenchymal stem cells (MSC) and enable image-guided cell implantation and longitudinal monitoring could advance MSC-based therapies for bone defects and injuries. Here we demonstrate a multifunctional nanoparticle system that delivers resveratrol (RESV) intracellularly to improve osteogenesis and enables photoacoustic imaging of MSCs. RESV-loaded nanoparticles (RESV-NPs), formulated from poly (lactic-co-glycolic) acid and iron oxide, enhanced the stability of RESV by 18-fold and served as photoacoustic tomography (PAT) contrast for MSCs. Pre-loading MSCs with RESV-NP upregulated RUNX2 expression with a resultant increase in mineralization by 27% and 45% compared to supplementation with RESV-NP and free RESV, respectively, in 2-dimensional cultures. When grown in polyethylene glycol-based hydrogels, MSCs pre-loaded with RESV-NPs increased the overall level and homogeneity of mineralization compared to those supplemented with free RESV or RESV-NP. The PAT detected RESV-NP-loaded MSCs with a resolution of 1500 cells/µL, which ensured imaging of MSCs upon encapsulation in a PEG-based hydrogel and implantation within the rodent cranium. Significantly, RESV-NP-loaded MSCs in hydrogels did not show PAT signal dilution over time or a reduction in signal upon osteogenic differentiation. This multifunctional NP platform has the potential to advance translation of stem cell-based therapies, by improving stem cell function and consistency via intracellular drug delivery, and enabling the use of a promising emerging technology to monitor cells in a clinically relevant manner.

Synchrotron XRF imaging of Alzheimer's disease basal ganglia reveals linear dependence of high-field magnetic resonance microscopy on tissue iron concentration.

BACKGROUND: Chemical imaging of the human brain has great potential for diagnostic and monitoring purposes. The heterogeneity of human brain iron distribution, and alterations to this distribution in Alzheimer's disease, indicate iron as a potential endogenous marker. The influence of iron on certain magnetic resonance imaging (MRI) parameters increases with magnetic field, but is under-explored in human brain tissues above 7 T. NEW METHOD: Magnetic resonance microscopy at 9.4 T is used to calculate parametric images of chemically-unfixed post-mortem tissue from Alzheimer's cases (n = 3) and healthy controls (n = 2). Iron-rich regions including caudate nucleus, putamen, globus pallidus and substantia nigra are analysed prior to imaging of total iron distribution with synchrotron X-ray fluorescence mapping. Iron fluorescence calibration is achieved with adjacent tissue blocks, analysed by inductively coupled plasma mass spectrometry or graphite furnace atomic absorption spectroscopy. RESULTS: Correlated MR images and fluorescence maps indicate linear dependence of R2, R2* and R2' on iron at 9.4 T, for both disease and control, as follows: [R2(s-1) = 0.072[Fe] + 20]; [R2*(s-1) = 0.34[Fe] + 37]; [R2'(s-1) = 0.26[Fe] + 16] for Fe in µg/g tissue (wet weight). COMPARISON WITH EXISTING METHODS: This method permits simultaneous non-destructive imaging of most bioavailable elements. Iron is the focus of the present study as it offers strong scope for clinical evaluation; the approach may be used more widely to evaluate the impact of chemical elements on clinical imaging parameters. CONCLUSION: The results at 9.4 T are in excellent quantitative agreement with predictions from experiments performed at lower magnetic fields.

Dendritic Cell-Activating Magnetic Nanoparticles Enable Early Prediction of Antitumor Response with Magnetic Resonance Imaging.

Cancer vaccines initiate antitumor responses in a subset of patients, but the lack of clinically meaningful biomarkers to predict treatment response limits their development. Here, we design multifunctional RNA-loaded magnetic liposomes to initiate potent antitumor immunity and function as an early biomarker of treatment response. These particles activate dendritic cells (DCs) more effectively than electroporation, leading to superior inhibition of tumor growth in treatment models. Inclusion of iron oxide enhances DC transfection and enables tracking of DC migration with magnetic resonance imaging (MRI). We show that T2*-weighted MRI intensity in lymph nodes is a strong correlation of DC trafficking and is an early predictor of antitumor response. In preclinical tumor models, MRI-predicted "responders" identified 2 days after vaccination had significantly smaller tumors 2-5 weeks after treatment and lived 73% longer than MRI-predicted "nonresponders". These studies therefore provide a simple, scalable nanoparticle formulation to generate robust antitumor immune responses and predict individual treatment outcome with MRI.