Magnetic nanoparticles in alternating magnetic fields (AMFs) transfer some of the field's energy to their surroundings in the form of heat, a property that has attracted significant attention for use ...in cancer treatment through hyperthermia and in developing magnetic drug carriers that can be actuated to release their cargo externally using magnetic fields. To date, most work in this field has focused on the use of AMFs that actuate heat release by nanoparticles over large regions, without the ability to select specific nanoparticle-loaded regions for heating while leaving other nanoparticle-loaded regions unaffected. In parallel, magnetic particle imaging (MPI) has emerged as a promising approach to image the distribution of magnetic nanoparticle tracers in vivo, with sub-millimeter spatial resolution. The underlying principle in MPI is the application of a selection magnetic field gradient, which defines a small region of low bias field, superimposed with an AMF (of lower frequency and amplitude than those normally used to actuate heating by the nanoparticles) to obtain a signal which is proportional to the concentration of particles in the region of low bias field. Here we extend previous models for estimating the energy dissipation rates of magnetic nanoparticles in uniform AMFs to provide theoretical predictions of how the selection magnetic field gradient used in MPI can be used to selectively actuate heating by magnetic nanoparticles in the low bias field region of the selection magnetic field gradient. Theoretical predictions are given for the spatial decay in energy dissipation rate under magnetic field gradients representative of those that can be achieved with current MPI technology. These results underscore the potential of combining MPI and higher amplitude/frequency actuation AMFs to achieve selective magnetic fluid hyperthermia (MFH) guided by MPI.
•SAR predictions based on a field-dependent magnetization relaxation model.•MPI field gradients can be used to achieve selective heating of nanoparticles.•Heating can be spatially-focused at length scales of millimeters to centimeters.
Image-guided treatment of cancer enables physicians to localize and treat tumors with great precision. Here, we present in vivo results showing that an emerging imaging modality, magnetic particle ...imaging (MPI), can be combined with magnetic hyperthermia into an image-guided theranostic platform. MPI is a noninvasive 3D tomographic imaging method with high sensitivity and contrast, zero ionizing radiation, and is linearly quantitative at any depth with no view limitations. The same superparamagnetic iron oxide nanoparticle (SPIONs) tracers imaged in MPI can also be excited to generate heat for magnetic hyperthermia. In this study, we demonstrate a theranostic platform, with quantitative MPI image guidance for treatment planning and use of the MPI gradients for spatial localization of magnetic hyperthermia to arbitrarily selected regions. This addresses a key challenge of conventional magnetic hyperthermiaSPIONs delivered systemically accumulate in off-target organs (e.g., liver and spleen), and difficulty in localizing hyperthermia results in collateral heat damage to these organs. Using a MPI magnetic hyperthermia workflow, we demonstrate image-guided spatial localization of hyperthermia to the tumor while minimizing collateral damage to the nearby liver (1–2 cm distance). Localization of thermal damage and therapy was validated with luciferase activity and histological assessment. Apart from localizing thermal therapy, the technique presented here can also be extended to localize actuation of drug release and other biomechanical-based therapies. With high contrast and high sensitivity imaging combined with precise control and localization of the actuated therapy, MPI is a powerful platform for magnetic-based theranostics.
Magnetic particle imaging (MPI) is a rapidly developing molecular and cellular imaging modality. Magnetic fluid hyperthermia (MFH) is a promising therapeutic approach where magnetic nanoparticles are ...used as a conduit for targeted energy deposition, such as in hyperthermia induction and drug delivery. The physics germane to and exploited by MPI and MFH are similar, and the same particles can be used effectively for both. Consequently, the method of signal localization through the use of gradient fields in MPI can also be used to spatially localize MFH, allowing for spatially selective heating deep in the body and generally providing greater control and flexibility in MFH. Furthermore, MPI and MFH may be integrated together in a single device for simultaneous MPI-MFH and seamless switching between imaging and therapeutic modes. Here we show simulation and experimental work quantifying the extent of spatial localization of MFH using MPI systems: we report the first combined MPI-MFH system and demonstrate on-demand selective heating of nanoparticle samples separated by only 3 mm (up to 0.4 °C s−1 heating rates and 150 W g−1 SAR deposition). We also show experimental data for MPI performed at a typical MFH frequency and show preliminary simultaneous MPI-MFH experimental data.
Nanoscaled drug carriers have been developed to accumulate in tumors and release a drug cargo either passively or in response to a local stimulus. However, strategies that rely on passive release or ...response to a local stimulus do not allow for spatial and temporal control of drug delivery. These limitations motivate interest in drug delivery platforms that release cargo in response to an external stimulus. This contribution describes magnetically controlled nanocarriers (MCNCs) that release heat and a drug cargo in response to an applied alternating magnetic field (AMF). The MCNCs consist of a hydrophobic core of superparamagnetic iron oxide nanoparticles that release heat in response to an AMF and a thermoresponsive polymer that releases a molecular cargo via breakage of thermally labile Diels–Alder (DA) bonds. The nanocarriers are coated with polyethylene glycol-block-polylactic acid (PEG4.9kD-PLA6.0kD) block copolymer to confer colloidal stability and water solubility. The MCNCs are assembled through flash nanoprecipitation, a rapid approach to making nanoparticles that is scalable and provides control of size and composition. Release experiments show that application of an AMF results in on-demand heat and drug release. The AMF-actuated release ceases when the field is turned off, and multiple applications of AMF result in programmable release. The amount of release is tunable via the AMF field strength and can be spatially controlled using selection magnetic field gradients. These results suggest that a potent combination of magnetic hyperthermia and drug release can be actuated in a desired region.
The design and validation of a magnetic particle spectrometer (MPS) system used to study the linear and nonlinear behavior of magnetic nanoparticle suspensions is presented. The MPS characterizes the ...suspension dynamic response, both due to relaxation and saturation effects, which depends on the magnetic particles and their environment. The system applies sinusoidal excitation magnetic fields varying in amplitude and frequency and can be configured for linear measurements (1 mT at up to 120 kHz) and nonlinear measurements (50 mT at up to 24 kHz). Time-resolved data acquisition at up to 4 MS/s combined with hardware and software-based signal processing allows for wide-band measurements up to 50 harmonics in nonlinear mode. By cross-calibrating the instrument with a known sample, the instantaneous sample magnetization can be quantitatively reconstructed. Validation of the two MPS modes are performed for iron oxide and cobalt ferrite suspensions, exhibiting Néel and Brownian relaxation, respectively.
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.
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).
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