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WIREs Nanomed Nanobiotechnol
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Principles and emerging applications of nanomagnetic materials in medicine

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Abstract The development of nanometer‐scale magnetic materials for biomedical applications spans the interface between the physical sciences and biology. Applications of these materials are rapidly becoming important in medicine and enable targeted therapies and diagnostics. At the same time, specific applications add focus to the development of novel magnetic materials and facilitate a deeper understanding of the physical mechanisms behind their function. This review presents a broad, nontechnical overview of the basis of magnetism in materials at the nanometer scale and describes how these materials are created, characterized, and used. Specific emerging applications in medical diagnostics and therapies are discussed, including cancer cell targeting for thermal ablation, tissue engineering, and three‐dimensional noninvasive molecular imaging. Challenges in these fields are discussed, including the toxicity and delivery of magnetic nanomaterials and the sensitivity of imaging and therapeutic techniques. The development of novel nanomagnetic nanomaterials should continue to accelerate as new applications are identified and researchers uncover new mechanisms to increase and modulate magnetism at the nanometer scale. WIREs Nanomed Nanobiotechnol 2012, 4:345–365. doi: 10.1002/wnan.1169 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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X‐ray diffraction spectra of Pd, Pd95W5, Pd80W20, and Pd70W30. Indicating typical Pd, and W peaks of different phases (a). Nanodiffraction patterns of horse spleen ferritin showing patterns resulting from maghemite‐like structure (b). Transmission electron microscopy (TEM) of magnetoferritin nanoparticles. Inset: high‐resolution electron microscopy (HREM) of a single magnetoferritin particle with lattice spacings corresponding to 2.5 Å (c). (a, Reproduced with permission from Ref 60. Copyright 2008 Royal Society of Chemistry; b, Reprinted with permission from Ref 61. Copyright 2000 Mineralogical Society of America; and c, Reprinted with permission from Ref 62. Copyright 2010 John Wiley & Sons, Inc.)

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M(T) curves for Co nanoparticles, sizes range from 3.9 to 13.1 nm. Peaks represent the transition temperature from ferromagnetic to superparamagnetic (a). Hysteresis loops demonstrating size effects on coercive fields for Co nanocrystals (b). (Reprinted with permission from Ref 54. Copyright 2002 John Wiley and Sons, Inc.)

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X‐ray diffraction (XRD) analysis and magnetic properties of CocorePtshell nanoparticles. (a) XRD pattern of CocorePtshell nanoparticles annealed at 700°C for 12 h. All peaks are well matched to reference fct Co1Pt1 alloys (dashed line). (b) Thermal alloying of CocorePtshell nanoparticles to anisotropic fct structure. Hysteresis loops of CocorePtshell nanoparticles measured at 300 K (c) before and (d) after the annealing process at 700°C. The magnetic coercivity of the nanoparticles is significantly enhanced from 0 to 5300 Oe exhibiting room‐temperature ferromagnetism. (Reprinted with permission from Ref 55. Copyright 2004 American Chemical Society)

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Transmission electron micrographs (TEMs) of porous hollow Au nanoparticles (PHAuNPs) before (a) and after (b) loading iron oxide nanoparticles. (Reprinted with permission from Ref 44. Copyright 2011 SpringerOpen journal)

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Ferrite spinel crystal structure illustrating possible octahedral (Oh) and tetrahedral (Th) dopant occupancy sites (a). (b) Unit cell spin moments for magnetically engineered ferrites with Mn2+, Fe2+/3+, Co2+, and Ni2+ doping. (c) Respective mass magnetization values for Mn‐, Fe‐, Co‐, and Ni‐doped ferrites and their relaxivity coefficients. (b and c: Reprinted with permission from Ref 7. Copyright 2007 Macmillan Publishers Ltd: Nature Publishing Group)

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Whole‐kidney identification of individual glomeruli. A representative axial kidney image from a 3D magnetic resonance imaging (MRI) dataset from a CF‐injected animal is shown (a). The data were analyzed with a 3D counting algorithm to identify individual glomeruli. Regions defined as glomeruli by the computational 3D counting algorithm were assigned an arbitrary color exclusively for visualization purposes (b). (Reprinted from Ref 135. Copyright 2011 The American Physiological Society)

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Images of dynamic magnetic particle imaging (MPI) fused with static magnetic resonance imaging (MRI). (a–e) Dynamic MPI images (left) and their fusion with static MRI images (acquisition time 23 min) in orthogonal views at selected points in time. The MPI video acquisition (21.5 ms per volume) started before injecting the tracer (Resovist) into the tail vein. The colored triangle in the overlay indicates the position of the orthogonal slices highlighted by the corresponding color frame. The position of the slices in the MRI volume is also given by the three numbers at the corners of the frames and is not always kept constant between the different images. The time axis on the right side describes the successive phases of the bolus passage. The spatial and temporal resolution enables resolution and identification of all heart chambers as well as parts of the vessel tree. (Reprinted with permission from Ref 111. Copyright 2009 IOP Publishing Ltd.)

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Biological utility of NMPs. Small molecule detection was demonstrated using the avidin–biotin system as a model. Biotinylated NMPs were mixed with varying amounts of avidin, which caused aggregation of NMPs and corresponding changes in T2 relaxation times. The high r2 relaxivity of NMPs enabled extremely sensitive detection (≈︁1 p M of avidin), whereas the detection sensitivity with Mn‐MNPs was ≈︁20‐fold lower (20 p M) (a). Cancer cells (SkBr3) targeted with HER2/neu‐specific NMPs could be detected in 1‐µL sample volumes, and the detection limit was near single‐cell level. The inset table compares the cellular relaxivities of different particle preparations (b). NMPs incorporating near‐infrared dyes (NMP‐VT680) were used as dual in vivo imaging agents. Mice received intravenous injections of NMP‐VT680 before undergoing both magnetic resonance imaging (MRI) and fluorescent‐mediated tomography (FMT). Due to large amounts of phagocytic cells, the liver (L) showed decreased signal intensity with MRI, while under FMT, the liver showed high fluorescent signals (c). (Reprinted with permission from Ref 106. Copyright 2011 John Wiley & Sons, Inc.)

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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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