Proteomic characterization of particle-protein coronas shows differences between osteoarthritic and contralateral knees in a rat model.

Objective: When synthetic particles are injected into a biofluid, proteins nonspecifically adsorb onto the particle surface and form a protein corona. Protein coronas are known to alter how particles function in blood; however, little is known about protein corona formation in synovial fluid or how these coronas change with osteoarthritis (OA). In this study, protein coronas were characterized on particles incubated within OA-affected or healthy rat knees.

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/β-catenin signaling is linked to cancer.

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.

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.

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.

Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(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 β-amyloid (Aβ) 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.

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.

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.

Evaluation of magnetic nanoparticles for magnetic fluid hyperthermia.

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.

Carbodiimide Conjugation of Latent Transforming Growth Factor β1 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-β) via magnetic hyperthermia by binding SPIONs to the latent form of TGF-β, since heat has been shown to induce release of TGF-β 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.

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.

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.

Magnetic nanoparticles loaded with functional RNA nanoparticles.

RNA is now widely acknowledged not only as a multifunctional biopolymer but also as a dynamic material for constructing nanostructures with various biological functions. Programmable RNA nanoparticles (NPs) allow precise control over their formulation and activation of multiple functionalities, with the potential to self-assemble in biological systems. These attributes make them attractive for drug delivery and therapeutic applications.

Alternating current (AC) susceptibility as a particle-focused probe of coating and clustering behaviour in magnetic nanoparticle suspensions.

Hypothesis: The functionality of magnetic nanoparticles (MNPs) relies heavily on their surface coating, which in turn affects the interactions between MNPs, and the formation of single-core particles or multi-core clusters. In this study we assessed the use of AC susceptibility (ACS) as a magnetic probe of the kinetics of coating and agglomeration of functionalised nanoparticles. We demonstrate the precision and sensitivity of ACS measurements to small changes in MNP coating using arginine-glycine-aspartic acid (RGD) tripeptide binding, and subsequently discuss how ACS can be used to optimise the preparation of polyethyleneimine (PEI) functionalised MNPs aimed at nanomagnetic transfection applications.

Nanoscale synchrotron X-ray speciation of iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects.

Altered metabolism of biometals in the brain is a key feature of Alzheimer's disease, and biometal interactions with amyloid-β are linked to amyloid plaque formation. Iron-rich aggregates, including evidence for the mixed-valence iron oxide magnetite, are associated with amyloid plaques. To test the hypothesis that increased chemical reduction of iron, as observed in vitro in the presence of aggregating amyloid-β, may occur at sites of amyloid plaque formation in the human brain, the nanoscale distribution and physicochemical states of biometals, particularly iron, were characterised in isolated amyloid plaque cores from human Alzheimer's disease cases using synchrotron X-ray spectromicroscopy.

Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.

A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ peptide can in part be explained by metal ion binding interactions.

Magnetic particle translation as a surrogate measure for synovial fluid mechanics.

The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100μL synovial fluid sample.

Oscillating Magnet Array-Based Nanomagnetic Gene Transfection: A Valuable Tool for Molecular Neurobiology Studies.

To develop treatments for neurodegenerative disorders, it is critical to understand the biology and function of neurons in both normal and diseased states. Molecular studies of neurons involve the delivery of small biomolecules into cultured neurons via transfection to study genetic variants. However, as cultured primary neurons are sensitive to temperature change, stress, and shifts in pH, these factors make biomolecule delivery difficult, particularly non-viral delivery.

Design and characterization of a magnetite/PEI multifunctional nanohybrid as non-viral vector and cell isolation system.

It is described the reproducible formulation and complete physicochemical characterization of nanohybrids based on magnetite (FeO) cores embedded within a polyethylenimine (PEI) matrix. Particle size, surface electrical charge, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) analyses, and magnetic field-responsive behaviour characterizations defined that the 4:3 (FeO:PEI) weight proportion led to the best production performances of magnetically responsive nanocomposites in which the magnetic nuclei are completely covered by the polymeric shell. Agarose gel electrophoresis assays demonstrated the capacity of the FeO/PEI particles to condense, release, and protect the DNA against enzymatic degradation.

Controlled release of a heterogeneous human placental matrix from PLGA microparticles to modulate angiogenesis.

A significant hurdle limiting musculoskeletal tissue regeneration is the inability to develop effective vascular networks to support cellular development within engineered constructs. Due to the inherent complexity of angiogenesis, where multiple biochemical pathways induce and control vessel formation, our laboratory has taken an alternate approach using a matrix material containing angiogenic and osteogenic proteins derived from human placental tissues. Single bolus administrations of the human placental matrix (hPM) have been shown to initiate angiogenesis but vascular networks deteriorated over time.

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.

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.

Directing cell therapy to anatomic target sites in vivo with magnetic resonance targeting.

Cell-based therapy exploits modified human cells to treat diseases but its targeted application in specific tissues, particularly those lying deep in the body where direct injection is not possible, has been problematic. Here we use a magnetic resonance imaging (MRI) system to direct macrophages carrying an oncolytic virus, Seprehvir, into primary and metastatic tumour sites in mice. To achieve this, we magnetically label macrophages with super-paramagnetic iron oxide nanoparticles and apply pulsed magnetic field gradients in the direction of the tumour sites.

Investigation of the Capture of Magnetic Particles From High-Viscosity Fluids Using Permanent Magnets.

Goal: This paper investigates the practicality of using a small, permanent magnet to capture magnetic particles out of high-viscosity biological fluids, such as synovial fluid.

Methods: Numerical simulations are used to predict the trajectory of magnetic particles toward the permanent magnet. The simulations are used to determine a "collection volume" with a time-dependent size and shape, which determines the number of particles that can be captured from the fluid in a given amount of time.