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Magnetic nanoparticles are attracting attention in biomedical applications due to their biocompatibility, tunable surface chemistry, and use of applied magnetic fields.
Magnetic nanoparticles respond to time-varying magnetic fields through the rotation of physical particles or internal dipole reorientation, which can lead to signal generation or conversion of magnetic energy into heat.
This dynamic magnetized response enables them to be used as tracers in magnetic particle imaging (MPI), an emerging biomedical imaging modality in which the signal is quantitative of tracer mass and there is no tissue background signal or signal attenuation.
The conversion of magnetic energy to thermal energy has driven the use of nanoscale thermal cancer treatment, magnetic drives for drug release, and rapid rewarming of cryopreserved organs.
This paper introduces the basic concepts of magnetic nanoparticle response to time-varying magnetic fields and introduces recent advances in the field, focusing on MPI and the conversion of magnetic energy into thermal energy.
Magnetic nanoparticles are functional nanomaterials of interest in established and emerging biomedical applications.
They can be manipulated by using applied constant and dynamic magnetic fields, and their response to these magnetic fields enables a wide range of applications.
Several reviews on the biomedical applications of magnetic nanoparticles have focused on their use as contrast agents for magnetic resonance (MR) imaging in tissue repair applications.
In this review, we focus on emerging biomedical applications that rely on the response of magnetic nanoparticles to time-varying magnetic fields.
In magnetic particle imaging (MPI), magnetic nanoparticle pairs can be based on alternating magnetic fields (AMFs) and select magnetic field gradients by using AMFs with higher amplitudes and frequencies.
Magnetic nanoparticles can be enabled to convert magnetic field energy into heat, which is transferred to their surroundings, a phenomenon that enables exciting emerging biomedical applications such as nanoscale thermal cancer therapy, remote initiation of drug delivery, and rapid volumetric rewarming of cryopreserved organs, which are discussed further below.
An attractive feature of magnetic nanoparticles is their translation record from laboratory to clinic.
US Food and Drug Administration approved iron oxide magnetic nanoparticles for the treatment of iron deficiency anemia in adults) and used by clinicians as an out-of-label MR imaging contrast agent, European Medicines Agency approved the use of iron oxide magnetic nanoparticles as MR contrast agent, magnetic nanoparticles are also approved in Europe for thermal therapy in glioblastoma, and are being studied in the US for the treatment of interstitial prostate cancer.
The clinical application of iron oxide magnetic nanoparticles has paved the way for current biomedical research seeking to take advantage of the unique magnetic properties of these materials.
Magnetic nanoparticles can be made from a variety of materials and compositions with adjustable size and morphology, which in turn determines their application-related physical and magnetic properties.
However, for biomedical applications requiring long-term contact with cells or tissues, toxicity and biocompatibility are primary considerations, which typically limit the composition to magnetite (Fe3O4) and magnetite (γ-Fe2O3) in the form of iron oxides.
and a subset of alternative ferrite nanoparticles, the formula is Mx (UK) Continuing Education 3−xO4, where metal M has no apparent toxicity.
For example, manganese, nickel or zinc-manganese ferrite has shown biocompatibility in preclinical studies, while nickel and zinc ferrite are non-toxic at low doses in vitro.
Superparamagnetic nanoparticles can be dispersed into aqueous solutions by surface modification using biocompatible polymers, resulting in ferrofluids suitable for biomedical applications.
When formulating magnetic nanoparticles for biomedical applications, avoid surface modification of magnetic nanoparticles due to van der Waals forces and magnetic forces to improve surface activity, enhance physicochemical properties and improve biocompatibility Biocompatible surface coatings can be made of polymeric materials [e.g..
Polyethylene glycol (PEG), dextran, polylactic acid means "combined" glycolic acid) and chitosan] and non-polymerized materials (e.g., surfactants and fatty acids, silica, gold).
Typical configurations of magnetic nanoparticles are shown, including mononuclear magnetic nanoparticles, polymer nanocomposites, magnetic liposomes, and magnetic micelles.
These coatings can be functionalized by using targeted ligands/proteins for active targeting, such as lactoferrin, transferrin, albumin, and TAT peptides, which can also bind to fluorophores for optical imaging and loaded with therapeutic drugs to increase circulation in the body and reduce side effects.
Other comprehensive reviews explain the biofunctionalization and surface chemistry of inorganic nanoparticles, the impact of protein corona formation on biological fate, and the impact of nanoparticle coatings on nanobiological interactions
In this review, we discuss their emerging biomedical applications based on the response of magnetic nanoparticles to magnetic fields.
Specifically, we cover (a) signal generation and (b) heat dissipation in response to time-varying magnetic fields through magnetic nanoparticles, as well as their related applications in biomedicine.
We briefly discuss the behavior of each class of iron oxide magnetic nanoparticles and how these specific magnetic responses can be used for emerging biomedical applications.
Magnetic nanoparticles have important practical significance because they have a so-called superparamagnetic response to magnetic fields, which results from magnetic ordering within the nanoscale magnetic domain.
At a sufficiently small size, magnetic materials such as magnetite and other iron oxides behave as single-domain magnets, whereby the magnetic dipole moments of the individual magnetic atoms act in unison, and the magnetic moments are orders of magnitude greater than the magnetic moments of the individual atoms.
This gives rise to the term superparamagnetic.
In general, the magnetic moment has a preferred orientation with respect to the crystal shaft (the so-called magnetizable shaft).
In order to change the direction of the magnetic moment, the energy barrier (i.e. magnetic anisotropy) must be overcome, which may be due to crystal properties (i.e. magnetic crystal anisotropy), shape, and surface effects.
In short, the response of magnetic nanoparticles to an applied magnetic field depends on the balance between magnetic field energy, thermal energy, and magnetic anisotropy.
Superparamagnetic corresponds to a state in which the energy barrier of the dipole moment rotation in the nanoparticle crystal is much smaller than the thermal energy, allowing the magnetic dipole of the single-domain particle to change direction quickly.
Due to the rapid random reorientation of magnetic dipoles, superparamagnetic nanoparticles show zero magnetization in the absence of a magnetic field, but are easily magnetized at relatively small magnetic fields.
This results in reversible magnetization behavior without hysteresis (zero remanence and coercivity) At low magnetic fields, the magnetization intensity increases linearly with the magnetic field, and the magnetic susceptibility is orders of magnitude greater than that of typical paramagnetic materials.
As the magnetic field strengthens, the magnetization eventually saturates, creating what is known as saturation magnetization.
Magnetite and magnetite exhibit superparamagnetism at the nanoscale and high saturation magnetization at 92 Am/kg and 76 Am/kg at 2293 K, respectively.
When single-domain magnetic nanoparticles are subjected to a time-varying magnetic field, the particle magnetic moment can respond through two different mechanisms, Nell relaxation or Brownian relaxation.
In the Nel relaxation, the magnetic moment will rotate within the particle crystal structure.
In contrast, in Brownian relaxation, where magnetic dipoles are fixed within the crystal structure, the whole particle will respond to AMF's understanding of the relative contribution of Brownian relaxation and Nell's relaxation to the magnetic field is important for obtaining nanoparticles optimized for each application, superparamagnetic iron oxide (SPIO) nanoparticles due to their stable physiological conditions, negligible toxicity, and high magnetic moment.
MPI is an emerging non-invasive tomography technique that can directly detect SPIO nanoparticle tracers.
Philips Research Laboratories invented magnetic resonance imaging in 2001; Grich-Wezenek reported the first system in 2005; Bruker BioSpin and Magnetic Insight began offering commercial scanners in 2013 and 2016, respectively.
Clinical scanners are under intense development, with the first prototype reported in 2019 and much of MPI's research to date has focused on hardware and software development, while the development of functional scanner prototypes and commercial preclinical scanners has paved the way for recent work leveraging MPI in a wide range of biomedical applications.
Below we review the latest applications of MPI.
In MPI, a uniform AMF with a frequency of typically 20–45 kHz and an amplitude of 10–16 mT is superimposed with a selective magnetic field gradient, resulting in a strong selective magnetic field gradient (3–7 t/m) at the field-free region (FFR) FR that sweeps rapidly across the field of view (FOV).
Therefore, choosing the magnitude of the magnetic field gradient can saturate the magnetic SPIOs outside the FFR.
Since the SPIOs in the FFR respond to the AMF by dipole redirection, resulting in a signal measured by the pickup coil around the FOV, an image of the magnetic nanoparticle distribution is produced.
In contrast, SPIOs other than FFR are saturated and do not respond significantly to AMF.
Due to the direct coupling between the AMF and the pickup coil, the fundamental frequency of the SPIO magnetization response cannot be reliably measured.
Therefore, MPI relies on the nonlinear magnetization response of nanoparticles to produce higher order harmonics.
Because the signal generated in the pickup coil is proportional to the mass of spio in the FFR, the constructed image provides a quantitative picture of the spio distribution in the FOV because normal tissues lack the superparamagnetic components with the necessary nonlinear magnetization response at the frequency and amplitude of the AMF.
So there is no tissue background signal in MPI, and in addition, the tissue attenuation of AMF and the resulting SPIO magnetization are negligible.
Therefore, MPI is not affected by tissue decay.
It is important to emphasize that the signal generation mechanism in MPI is different from the contrast generation mechanism of SPIOs in MR imaging.
MR uses a uniform external magnetic field (0.2–7T) to arrange the magnetic moments of protons in tissues.
Differences in tissue proton relaxation to magnetic fields and radio waves are used to generate detailed anatomical images.
SPIOs create contrast in MR imaging by introducing local inhomogeneities in the magnetic field experienced by tissue protons.
The result is a low-intensity or negative contrast signal in areas where SPIOs are clustered.
These features make it difficult to reliably quantify SPIO concentrations using MR imaging.
Furthermore, because other anatomical features can result in low-intensity signals similar to SPIOs, reliable identification of the location of SPIOs in a sample requires prior knowledge of the MR signal of the tissue in question.
Finally, the different physical mechanisms of signal generation in MR imaging and MPI suggest that spio optimized for MR imaging is not necessarily suitable for MPI, which highlights the need for new spios tailored for MPI sensitivity and resolution.
Although relying on the same basic hardware and physics, two main methods of image reconstruction are used in MPI.
In harmonic space, MPI uses the harmonic amplitude obtained by calculating the Fourier transform of the time-dependent magnetization of the tracer.
In order to generate a system matrix with the spectral response of tracer positions within the FOV, the subsequent use of matrix inversion technique to harmonic space MPI SPIO tracer performance is characterized by obtaining tracer harmonic spectra under conditions similar to those used to acquire MPI images in x-space MPI.