Superferromagnetic Nanoparticles Enable Order-of-Magnitude Resolution & Sensitivity Gain in Magnetic Particle Imaging.

Magnetic nanoparticles have many advantages in medicine such as their use in non-invasive imaging as a Magnetic Particle Imaging (MPI) tracer or Magnetic Resonance Imaging contrast agent, the ability to be externally shifted or actuated and externally excited to generate heat or release drugs for therapy. Existing nanoparticles have a gentle sigmoidal magnetization response that limits resolution and sensitivity. Here it is shown that superferromagnetic iron oxide nanoparticle chains (SFMIOs) achieve an ideal step-like magnetization response to improve both image resolution & SNR by more than tenfold over conventional MPI. The underlying mechanism relies on dynamic magnetization with square-like hysteresis loops in response to 20 kHz, 15 kAm-1 MPI excitation, with nanoparticles assembling into a chain under an applied magnetic field. Experimental data shows a "1D avalanche" dipole reversal of every nanoparticle in the chain when the applied field overcomes the dynamic coercive threshold of dipole-dipole fields from adjacent nanoparticles in the chain. Intense inductive signal is produced from this event resulting in a sharp signal peak. Novel MPI imaging strategies are demonstrated to harness this behavior towards order-of-magnitude medical image improvements. SFMIOs can provide a breakthrough in noninvasive imaging of cancer, pulmonary embolism, gastrointestinal bleeds, stroke, and inflammation imaging.

Fast nanoparticle rotational and translational diffusion in synovial fluid and hyaluronic acid solutions.

Nanoparticles are under investigation as diagnostic and therapeutic agents for joint diseases, such as osteoarthritis. However, there is incomplete understanding of nanoparticle diffusion in synovial fluid, the fluid inside the joint, which consists of a mixture of the polyelectrolyte hyaluronic acid, proteins, and other components. Here, we show that rotational and translational diffusion of polymer-coated nanoparticles in quiescent synovial fluid and in hyaluronic acid solutions is well described by the Stokes-Einstein relationship, albeit with an effective medium viscosity that is much smaller than the macroscopic low shear viscosity of the fluid. This effective medium viscosity is well described by an equation for the viscosity of dilute polymer chains, where the additional viscous dissipation arises because of the presence of the polymer segments. These results shed light on the diffusive behavior of polymer-coated inorganic nanoparticles in complex and crowded biological environments, such as in the joint.

Long circulating tracer tailored for magnetic particle imaging.

Superparamagnetic iron oxide nanoparticle (SPION) tracers possessing long blood circulation time and tailored for magnetic particle imaging (MPI) performance are crucial for the development of this emerging molecular imaging modality. Here, single-core SPION MPI tracers coated with covalently bonded polyethyelene glycol (PEG) brushes were obtained using a semi-batch thermal decomposition synthesis with controlled addition of molecular oxygen, followed by an optimized PEG-silane ligand exchange procedure. The physical and magnetic properties, MPI performance, and blood circulation time of these newly synthesized tracers were compared to those of two commercially available SPIONs that were not tailored for MPI but are used for MPI: ferucarbotran and PEG-coated Synomag®-D. The new tailored tracer has MPI sensitivity that is ~3-times better than the commercial tracer ferucarbotran and much longer circulation half-life than both commercial tracers (t1/2=6.99 h for the new tracer, vs t1/2=0.59 h for ferucarbotran, and t1/2=0.62 h for PEG-coated Synomag®-D).

Theranostic nanocarriers combining high drug loading and magnetic particle imaging.

We report preparation of theranostic nanocarriers loaded with up to 50 wt% of the anticancer drug doxorubicin that contain magnetic nanoparticles which enable Magnetic Particle Imaging (MPI), an emerging technology for quantitative and unambiguous imaging of the nanocarriers. The nanocarriers, coated with poly(ethylene glycol)-block-poly(lactic acid) (PEG4.9kD-b-PLA6kD) block copolymer for colloidal stability, are composed of a hydrophobic core of precipitated hydrolysable doxorubicin prodrug (proDox) and magnetic nanoparticles. Transmission electron microscopy (TEM) shows evidence of precipitated proDox for nanocarriers with high drug loading of up to 50 wt%. MPI measurements show that the nanocarriers can be quantitatively imaged. The nanocarriers are internalized by MDA-MB-231 cells and their IC50 value via metabolic assay is 1.1 µM, compared to 0.21 µM for free doxorubicin. The release rate from the nanocarriers was dependent on environmental pH. These nanocarriers with high drug loading and quantitative imaging are promising candidates for future applications.

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.

Benchtop magnetic particle relaxometer for detection, characterization and analysis of magnetic nanoparticles.

This paper presents the design, construction, and testing of a magnetic particle relaxometer (MPR) to assess magnetic nanoparticle response to dynamic magnetic fields while subjected to a bias field. The designed MPR can characterize magnetic particles for use as tracers in magnetic particle imaging (MPI), with the variation of an applied bias field emulating the scan of the MPI field free point. The system applies a high-frequency time-varying excitation field (up to 45 mT at 30 kHz), while slowly ramping a bias field (±100 mT in 1 s). The time-resolved response of the sample is measured using an inductive sensing coil system, made of a pick-up coil and a rotating and translating balancing coil to finely cancel the induction feed-through from the excitation field. A post-processing algorithm is presented to extract the tracer response related to the point spread function for MPI applications, and the performance of the MPR is demonstrated using superparamagnetic iron oxide particles (ferucarbotran).

Thermal Decomposition Synthesis of Iron Oxide Nanoparticles with Diminished Magnetic Dead Layer by Controlled Addition of Oxygen.

Decades of research focused on size and shape control of iron oxide nanoparticles have led to methods of synthesis that afford excellent control over physical size and shape but comparatively poor control over magnetic properties. Popular synthesis methods based on thermal decomposition of organometallic precursors in the absence of oxygen have yielded particles with mixed iron oxide phases, crystal defects, and poorer than expected magnetic properties, including the existence of a thick "magnetically dead layer" experimentally evidenced by a magnetic diameter significantly smaller than the physical diameter. Here, we show how single-crystalline iron oxide nanoparticles with few defects and similar physical and magetic diameter distributions can be obtained by introducing molecular oxygen as one of the reactive species in the thermal decomposition synthesis. This is achieved without the need for any postsynthesis oxidation or thermal annealing. These results address a significant challenge in the synthesis of nanoparticles with predictable magnetic properties and could lead to advances in applications of magnetic nanoparticles.