Cindi L. Dennis

Physics of heat generation using magnetic nanoparticles for hyperthermia

Abstract Magnetic nanoparticle hyperthermia and thermal ablation have been actively studied experimentally and theoretically. In this review, we provide a summary of the literature describing the properties of nanometer-scale magnetic materials suspended in biocompatible fluids and their interactions with external magnetic fields. Summarised are the properties and mechanisms understood to be responsible for magnetic heating, and the models developed to understand the behaviour of single-domain magnets exposed to alternating magnetic fields. Linear response theory and its assumptions have provided a useful beginning point; however, its limitations are apparent when nanoparticle heating is measured over a wide range of magnetic fields. Well-developed models (e.g. for magnetisation reversal mechanisms and pseudo-single domain formation) available from other fields of research are explored. Some of the methods described include effects of moment relaxation, anisotropy, nanoparticle and moment rotation mechanisms, interactions and collective behaviour, which have been experimentally identified to be important. Here, we will discuss the implicit assumptions underlying these analytical models and their relevance to experiments. Numerical simulations will be discussed as an alternative to these simple analytical models, including their applicability to experimental data. Finally, guidelines for the design of optimal magnetic nanoparticles will be presented.

Controlling the Self‐Assembly of Metal‐Seamed Organic Nanocapsules

The advent of modern molecular characterization techniques in the mid 20th century brought about a renaissance in our understanding of life s many processes. Notably, the structural determination of large biomolecules through the development of techniques such as NMR spectroscopy and X-ray diffraction (XRD) has given scientists valuable insight into the inner workings of cells. Many of these molecules are highly symmetrical, multicomponent entities, though determining the processes by which they assemble has been a difficult task. The biosynthesis of DNA, for example, came much later than its structural characterization by Watson and Crick. It is exactly this knowledge, however, that allows one to control the system. Supramolecular chemists have likewise endeavored to control the self-assembly processes in multicomponent entities. Although simpler than many biomolecules, the size and complexity of the macromolecules that embody this field largely preclude the use of standard mechanistic analyses that are applicable to smaller compounds. Our work has focused on metal-seamed pyrogallol[4]arene (PgC) nanocapsules. Forming rapidly through selfassembly, these large entities are composed of 2 or 6 macrocyclic units that act as chelates through their upper rims for 8, 12, or 24 metal ions (Figure 1). It is important to note that the 6-macrocycle, 24-metal ion hexameric nanocapsule results from the remarkable self-assembly of 30 entities. The dimeric or hexameric capsules are highly sym-

The influence of collective behavior on the magnetic and heating properties of iron oxide nanoparticles

Magnetic nanoparticles with a high specific absorption rate (SAR) have been developed and used in mouse models of cancer. The magnetic nanoparticles are comprised of predominantly iron oxide magnetic cores surrounded by a dextran layer for colloidal stability. The average diameter of a single particle (core plus dextran) is 92±14nm as measured by photon correlation spectroscopy. Small angle neutron scattering measurements under several H2O∕D2O contrast conditions and at varying nanoparticle concentrations have revealed three length scales: >10μm, several hundred nanometers, and tens of nanometers. The latter corresponds to the particle diameter; the several hundred nanometers corresponds to a hard sphere interaction radius of the core/shell nanoparticles; >10μm corresponds to the formation of long-range, many-particle structures held together by magnetic interactions and dextran. The long-range collective magnetic behavior appears to play a major role in enhancing the SAR. For samples having nominally equ...

The influence of magnetic and physiological behaviour on the effectiveness of iron oxide nanoparticles for hyperthermia

Magnetic nanoparticles are being developed for a wide range of biomedical applications. In particular, hyperthermia involves heating the magnetic nanoparticles through exposure to an alternating magnetic field. These materials offer the potential to selectively treat cancer by heating cancer tissue locally and at the cellular level. This may be a successful method if there are enough particles in a tumor possessing a sufficiently high specific absorption rate (SAR) to deposit heat quickly while minimizing thermal damage to surrounding tissue. High SAR magnetic nanoparticles have been developed and used in mouse models of cancer. The magnetic nanoparticles comprise iron oxide magnetic cores (mean core diameter of 50 nm) surrounded by a dextran layer shell for colloidal stability. In comparing two similar systems, the saturation magnetization is found to play a crucial role in determining the SAR, but is not the only factor of importance. (A difference in saturation magnetization of a factor of 1.5 yields a difference in SAR of a factor of 2.5 at 1080 Oe and 150 kHz.) Variations in the interactions due to differences in the dextran layer, as determined through neutron scattering, also play a role in the SAR. Once these nanoparticles are introduced into the tumor, their efficacy, with respect to tumor growth, is determined by the location of the nanoparticles within or near the tumor cells and the association of the nanoparticles with the delivered alternating magnetic field (AMF). This association (nanoparticle SAR and AMF) determines the amount of heat generated. In our setting, the heat generated and the time of heating (thermal dose) provides a tumor gross treatment response which correlates closely with that of conventional (non-nanoparticle) hyperthermia. This being said, it appears specific aspects of the nanoparticle hyperthermia cytopathology mechanism may be very different from that observed in conventional cancer treatment hyperthermia.

Multicore Magnetic Nanoparticles for Magnetic Particle Imaging

Biocompatible magnetic nanoparticles are interesting tracers for diagnostic imaging techniques, including magnetic resonance imaging and magnetic particle imaging (MPI). Here, we will present our studies of the physical and especially magnetic properties of dextran coated multicore magnetic iron oxide nanoparticles, with promising high MPI signals revealed by magnetic particle spectroscopy (MPS) measurements. The Nanomag-MIP particles with a hydrodynamic diameter of 106 nm show an increase of the MPS amplitude by a factor of about two at the 3rd harmonic, as compared to Resovist. In particular, the signal improves progressively with the order of the harmonic, a prerequisite for better spatial resolution. To understand this behavior, we investigated the samples using quasistatic magnetization measurements yielding bimodal size distributions for both systems, and magnetorelaxometry providing the mean effective anisotropy constant. The mean effective magnetic diameter of the dominant larger size mode is 19 nm with a dispersion parameter of σ = 0.3 for Nanomag-MIP, and 22 nm with σ = 0.25 for Resovist. However, about 80% of the magnetic nanoparticles of Nanomag-MIP belong to this larger size mode whereas in Resovist only 30% do. The remaining Resovist particles are in the range of 5 nm, and, in practice, do not contribute to the MPI signal.

Controlling high coercivities of ferromagnetic nanowires encapsulated in carbon nanotubes

Cylindrical ferromagnetic nanowires encapsulated inside multiwalled carbon nanotubes (MWNTs) are synthesized by pyrolyzing either ferrocene powder or ferrocene–toluene mixtures. By changing the way the precursor is thermolyzed, we have been able to control the composition of the ferromagnetic byproducts. In particular, we noted the coexistence of α-Fe and Fe3C phases when only powder ferrocene is theromolyzed in an inert atmosphere. However, when toluene–ferrocene solutions are sprayed and thermolyzed, only Fe3C nanocrystals are produced. Magnetic measurements of the aligned nanotubes containing these cylindrical nanowires revealed large coercive fields as high as 0.22 T at 2 K. Interestingly, these magnetic coercivities strongly depend on the Fe particles’ diameter, and are not affected by the length of the particles, which was also confirmed using micromagnetic simulations. Our experimental and theoretical results indicate that short and well aligned carbon nanotubes containing narrow ferromagnetic nanowires (i.e. 5 nm diameter and 25 nm long) would be suitable for producing prototypes of magnetic recording devices.

Exploring the magnetic behavior of nickel-coordinated pyrogallol[4]arene nanocapsules.

The magnetic behavior of nickel-seamed C-propylpyrogallol[4]arene dimeric and hexameric nanocapsular assemblies has been investigated in the solid state using a SQUID magnetometer. These dimeric and hexameric capsular entities show magnetic differentiation both in terms of moment per nanocapsule and potential antiferromagnetic interactions within individual nanocapsules. The weak antiferromagnetic behavior observed at low temperatures indicates dipolar interactions between neighboring nickel atoms; however, this effect is higher in the hexameric nickel-seamed assembly. The differences in magnetic behavior of dimer versus hexamer can be attributed to different coordination environments and metal arrangements in the two nanocapsular assemblies.

Magnetic differentiation of pyrogallol[4]arene tubular and capsular frameworks.

The differences in magnetic properties of metal-based nanometric assemblies are due to distinct contributions from host-guest interactions, structural integrity, and magnetic interactions. To disentangle these contributions, it is necessary to control the self-assembly process that forms these entities. Herein we study the effect of host-to-guest ratios to identify remarkably different structural-magnetic contributions of C-methylpyrogallol[4]arene⊂ferrocene/(PgC1)2⊂Fc dimers vs (PgC1)3⊂Fc nanotubes. At low temperature, a weak anti-ferromagnetic alignment is observed, suggesting a weak dipolar interaction between Fc guest moieties within adjacent dimers or tubes. Also, differences are observed between magnetic atom occupancy as a function of guest (PgC1⊂Fc tube/dimer) versus magnetic atom occupancy within the framework wall (PgC3Ni hexamer/dimer). Identification of the role of the framework shape and metal-metal distances in the crystal lattice opens up unparalleled prospects for materials engineering.

Effect of grain constraint on the field requirements for magnetocaloric effect in Ni45Co5Mn40Sn10 melt-spun ribbons

The influence of grain constraint on the magnetic field levels required to complete the isothermal martensitic transformation in magnetic shape memory alloys has been demonstrated for a NiCoMnSn alloy, and the magnetocaloric performance of an optimally heat treated alloy was quantified. Ni45CoxMn45-xSn10 melt spun ribbons with x = 2, 4, 5, and 6 were characterized. The x = 5 sample was determined to exhibit the lowest transformation thermal hysteresis (7 K) and transformation temperature range during transformation from paramagnetic austenite to nonmagnetic martensite, as well as a large latent heat of transformation (45 J kg-1 K-1). For this composition, it was found that increasing the grain size to thickness ratio of the ribbons from 0.2 to 1.2, through select heat treatments, resulted in a decrease in the magnetic field required to induce the martensitic transformation by about 3 T due to the corresponding reduction in the martensitic transformation temperature range. This decrease in the field requirement ultimately led to a larger magnetocaloric entropy change achieved under relatively smaller magnetic field levels. The giant inverse magnetocaloric effect of the optimized alloy was measured and showed that up to 25 J kg-1 K-1 was generated by driving the martensitic transition with magnetic fields up to 7 T.

Solution-phase and magnetic approach towards understanding iron gall ink-like nanoassemblies.

The degradative oxidation of Leonardo da Vinci s oeuvre, the works of Galileo, and many other imperiled ancient manuscripts is, ironically, catalyzed by the very ink that was used to write them. Historical artifacts such as these are characterized by the extensive use of “iron gall ink”, an ink commonly used prior to the twentieth century. Regardless of the specific composition, iron gall inks are complexes of various polyphenolic gallic acids, a class of tannins, and ferric/ ferrous ions, along with other agents such as gypsum and gum arabic. In the interest of preserving such invaluable works of ancient prose, Fe complexes with polyphenolic compounds, such as gallic acid, catechin, ellagic acid and pyrogallol, have been extensively studied by IR, ESR, NMR, XANES and Mçssbauer spectroscopy. However, structural elucidation of these complexes has proven difficult. Our interest in this field stems from the difficulty in characterizing similar Fe-polyphenolic complexes, namely the complexes with the bowlshaped pyrogallol[4]arenes (PgCn, n = alkyl chain length). Compared to other PgC-transition metal capsular entities, which have been thoroughly studied and characterized by XRD, the structure of the PgCnFe complexes has largely remained a mystery, much like that of the chemically similar gall inks. Herein, we present a new approach towards the characterization of these unique complexes through the combination of solid-state magnetic and in situ neutron scattering methods. In our previous studies, solid-state properties aided our understanding of solution-phase behavior. For example, solid-state PgCnM entities (M = Zn, Cu, Ni, Co) are spherical, and our small-angle neutron scattering (SANS) experiments indicate that they retain that architecture when dissolved in non-polar solvents. In contrast, solid-state PgC4Ga and PgC4GaZn entities have rugby-ball and spherical shapes, respectively, which convert to toroids of different metric dimensions in solution. Thus, SANS allows differentiation between architectures of similar metric dimensions and between varying metric dimensions of similar architectures. 6] The current study addresses our three-fold interest in investigating solution structures of magnetically interesting self-assembled frameworks, obtaining solid-state insight from solution-phase studies and exploring the parameters that direct self-assembly. Specifically, the stability, elemental ratios and magnetic properties of Fe-containing C-alkylpyrogallol[4]arene (PgCnFe) nanoassemblies were examined. PgC1Fe or PgC3Fe was synthesized by mixing 4 equiv of Fe(NO3)3 with 1 equiv of PgCn and 14 equiv of C5H5N (Py) in a variety of solvent systems. The blue-black precipitates obtained could not be crystallized; thus, structural studies were conducted using SANS. The solid-state magnetic behavior of these entities was investigated using a SQUID magnetometer. The composition of these nanoframeworks was measured with prompt gamma activation analysis (PGAA). The PGAA results for solid-state PgC1Fe and PgC3Fe reveal C:Fe ratios of 27.8:1 and 28.5:1 and C:N ratios of 28.1:1 and 29.2:1, respectively (see Supporting Information). The 1:1 ratio between Fe and C5H5N-derived nitrogen agrees with the metal:Py ratios typically found in metal-seamed pyrogallol[4]arene dimeric host capsules. However, in contrast to the typical capsular metal:PgCn ratio of 4:1, the Fe:PgCn ratio was unexpectedly deduced to be 1.3:1. This ratio also differs from those for the tubular and dimeric PgC1 ferrocene (PgC1 Fc) hydrogen-bonded inclusion complexes, for which the Fc:PgC1 ratios are 1:3 and 1:2, respectively. [4c,7] In the SANS study, the [D6]DMSO-solubilized PgC1Fe (3% mass fraction) was measured on the NG7 30 m SANS instrument at the NIST Center for Neutron Research (NCNR) in Gaithersburg, MD and analyzed with IGOR Pro. The scattering length density (SLD) of PgC1Fe was calculated at the molar ratio of 1:1.3:1.3 (PgC1:Fe:Py) obtained from the PGAA results, and the scattering data was fitted to spherical, cylindrical and ellipsoidal models. The data analysis revealed distinct structural differences between previously investigated metal-seamed spherical nanoassemblies and the Fe-containing pyrogallol[4]arene nanoassemblies (Figure 1). The scattering for PgC1Fe was higher at low scattering angles (q) and fitted [*] Dr. H. Kumari, A. V. Mossine, Prof. C. A. Deakyne, Prof. J. L. Atwood Department of Chemistry, University of Missouri-Columbia 601 S. College Avenue, Columbia, MO 65211 (USA) E-mail: deakynec@missouri.edu atwoodj@missouri.edu