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.
Lysosomal death pathways are being explored as alternatives of overcoming cancer tumor resistance to traditional forms of treatment. Nanotechnologies that can selectively target and induce ...permeabilization of lysosomal compartments in cells could become powerful medical tools. Here we demonstrate that iron oxide magnetic nanoparticles (MNPs) targeted to the epidermal growth factor receptor (EGFR) can selectively induce lysosomal membrane permeabilization (LMP) in cancer cells overexpressing the EGFR under the action of an alternating magnetic field (AMF). LMP was observed to correlate with the production of reactive oxygen species (ROS) and a decrease in tumor cell viability. Confocal microscopy images showed an increase in the cytosolic activity of the lysosomal protease cathepsin B. These observations suggest the possibility of remotely triggering lysosomal death pathways in cancer cells through the administration of MNPs which target lysosomal internalization pathways and the application of AMFs.
Iron oxide nanoparticles are of interest in a wide range of biomedical applications due to their response to applied magnetic fields and their unique magnetic properties. Magnetization measurements ...in constant and time-varying magnetic field are often carried out to quantify key properties of iron oxide nanoparticles. This chapter describes the importance of thorough magnetic characterization of iron oxide nanoparticles intended for use in biomedical applications. A basic introduction to relevant magnetic properties of iron oxide nanoparticles is given, followed by protocols and conditions used for measurement of magnetic properties, along with examples of data obtained from each measurement, and methods of data analysis.
We report observations of breakdown of the Stokes–Einstein relation for the rotational diffusivity of polymer-grafted spherical nanoparticles in polymer melts. The rotational diffusivity of magnetic ...nanoparticles coated with poly(ethylene glycol) dispersed in poly(ethylene glycol) melts was determined through dynamic magnetic susceptibility measurements of the collective rotation of the magnetic nanoparticles due to imposed time-varying magnetic torques. These measurements clearly demonstrate the existence of a critical molecular weight for the melt polymer, below which the Stokes–Einstein relation accurately describes the rotational diffusivity of the polymer-grafted nanoparticles and above which the Stokes–Einstein relation ceases to apply. This critical molecular weight was found to correspond to a chain contour length that approximates the hydrodynamic diameter of the nanoparticles.
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.
Clinical studies have demonstrated the effectiveness of hyperthermia as an adjuvant for chemotherapy and radiotherapy. However, significant clinical challenges have been encountered, such as a ...broader spectrum of toxicity, lack of patient tolerance, temperature control and significant invasiveness. Hyperthermia induced by magnetic nanoparticles in high-frequency oscillating magnetic fields, commonly termed magnetic fluid hyperthermia, is a promising form of heat delivery in which thermal energy is supplied at the nanoscale to the tumor. This review discusses the mechanisms of heat dissipation of iron oxide-based magnetic nanoparticles, current methods and challenges to deliver heat in the clinic, and the current work related to the use of magnetic nanoparticles for the thermal-chemopotentiation of therapeutic drugs.
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.
Abstract
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).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 °C due to energy dissipation in an alternating magnetic field. On ...the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential of MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.
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.
Magnetic particle imaging (MPI) is a new imaging method different from Magnetic Resonance Imaging that enables tracer‐like imaging of magnetic nanoparticles. This work demonstrates how superferromagnetism in a linear chain of iron oxide nanoparticles (SFMIOs) can be harnessed to improve MPI image spatial resolution and sensitivity tenfold. SFMIO potentially enables more sensitive and accurate cancer, vascular, and stem cell imaging.
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