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WIREs Nanomed Nanobiotechnol
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Use of magnetic fields and nanoparticles to trigger drug release and improve tumor targeting

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Abstract Drug delivery strategies aim to maximize a drug's therapeutic index by increasing the concentration of drug at target sites while minimizing delivery to off‐target tissues. Because biological tissues are minimally responsive to magnetic fields, there has been a great deal of interest in using magnetic nanoparticles in combination with applied magnetic fields to selectively control the accumulation and release of drug in target tissues while minimizing the impact on surrounding tissue. In particular, spatially variant magnetic fields have been used to encourage accumulation of drug‐loaded magnetic nanoparticles at target sites, while time‐variant magnetic fields have been used to induce drug release from thermally sensitive nanocarriers. In this review, we discuss nanoparticle formulations and approaches that have been developed for magnetic targeting and/or magnetically induced drug release, as well as ongoing challenges in using magnetism for therapeutic applications. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Magnetic fields and nanoparticles are used to improve drug delivery, particularly in cancer. Time‐variant magnetic fields can induce drug release from temperature‐sensitive drug carriers via magnetic heating (left). Space‐variant magnetic fields can improve drug accumulation in target tissues via magnetic drug targeting (right)
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Strong static fields containing field‐free regions can be used to target alternating magnetic fields for magnetic heating and drug release. (a) In the low‐field region, magnetic nanoparticles respond to the applied alternating magnetic field (AMF) to generate heat. Outside of the field‐free region, the nanoparticles are “pinned” in the direction of the static field, preventing their response to the AMF and thereby suppressing heating. (b) Static fields containing field‐free regions have been used for high‐resolution magnetic particle imaging and targeted tissue ablation via magnetic hyperthermia. (Reprinted with permission from Tay et al., . Copyright 2018 American Chemical Society) (c) By adding a third magnet, it is possible to independently control the size and location of the field‐free targeting region. (Reprinted with permission from J. F. Liu et al. (). Copyright 2018 John Wiley and Sons)
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Novel magnetic targeting device designs. (a) Halbach arrays can be used to achieve higher targeting fields compared to single magnets. The configuration of magnets in a Halbach array leads to a “strong” side with high magnetic fields, and a “weak” side where most of the field has been cancelled. (b) A steel yoke design can be used to achieve extremely high magnetic fields within a small area by “concentrating” the magnetic field lines. (Reprinted with permission from Voronin et al. (). Copyright 2017 American Chemical Society) (c) Recently, Krzyminiewski et al. have developed a system of rotating magnets to localize magnetic nanoparticles away from the surface of the device. (Reprinted with permission from Krzyminiewski, Dobosz, Schroeder, and Kurczewska (). Copyright 2018 Elsevier)
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Magnetic drug targeting of magnetic nanoparticle‐loaded liposomes has been used to target glioblastoma in mice. Upon exposure to a 0.4‐T external magnet, the iron oxide nanoparticle‐loaded liposomes localized to the tumor in an orthotopic U87 glioblastoma mouse model (left). In contrast, in the absence of the external magnetic targeting field, fewer nanocarriers accumulated in the tumor (right). Scale = 1 mm. (Reprinted with permission from Marie et al. (). Copyright 2015 John Wiley and Sons)
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Controlled addition of oxygen during thermal decomposition results in synthesis of particles with improved magnetic properties. (a) In the absence of oxygen, the physical diameter of the nanoparticles is well controlled. However, the magnetic diameter (Dm) of the particles is smaller and more polydisperse than the physical diameter (Dp). (b) When oxygen is added in a controlled manner to the synthesis, the physical and magnetic diameters of the particles is similar, leading to a threefold increase in the specific absorption rate of the particles. (Reprinted with permission from Unni et al. (). Copyright 2017 American Chemical Society)
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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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