Challenges and recommendations for magnetic hyperthermia characterization measurements

PURPOSE: The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields - a process known as magnetic field hyperthermia (MFH) - can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating - characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg - is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. MATERIALS AND METHODS: An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing. RESULTS: The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. CONCLUSION: We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology

Thermosensitive polymer-grafted iron oxide nanoparticles studied by in situ dynamic light backscattering under magnetic hyperthermia

© 2015 IOP Publishing Ltd. Thermometry at the nanoscale is an emerging area fostered by intensive research on nanoparticles (NPs) that are capable of converting electromagnetic waves into heat. Recent results suggest that stationary gradients can be maintained between the surface of NPs and the bulk solvent, a phenomenon sometimes referred to as \u27cold hyperthermia\u27. However, the measurement of such highly localized temperatures is particularly challenging. We describe here a new approach to probing the temperature at the surface of iron oxide NPs and enhancing the understanding of this phenomenon. This approach involves the grafting of thermosensitive polymer chains to the NP surface followed by the measurement of macroscopic properties of the resulting NP suspension and comparison to a calibration curve built up by macroscopic heating. Superparamagnetic iron oxide NPs were prepared by the coprecipitation of ferrous and ferric salts and functionalized with amines, then azides using a sol-gel route followed by a dehydrative coupling reaction. Thermosensitive poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) with an alkyne end-group was synthesized by controlled radical polymerization and was grafted using a copper assisted azide-alkyne cycloaddition reaction. Measurement of the colloidal properties by dynamic light scattering (DLS) indicated that the thermosensitive NPs exhibited changes in their Zeta potential and hydrodynamic diameter as a function of pH and temperature due to the grafted PDMAEMA chains. These changes were accompanied by changes in the relaxivities of the NPs, suggesting application as thermosensitive contrast agents for magnetic resonance imaging (MRI). In addition, a new fibre-based backscattering setup enabled positioning of the DLS remote-head as close as possible to the coil of a magnetic heating inductor to afford in situ probing of the backscattered light intensity, hydrodynamic diameter, and temperature. This approach provides a promising platform for estimating the response of magnetic NPs to application of a radiofrequency magnetic field or for understanding the behaviour of other thermogenic NPs

Particle interactions in liquid magnetic colloids by zero field cooled measurements: effects on heating efficiency

The influence of magnetic interactions in assemblies formed by either aggregated or disaggregated uniform gamma-Fe_2O_3 particles are investigated as a function of particle size, concentration, and applied field. Hyperthermia and magnetization measurements are performed in the liquid phase of colloids consisting of 8 and 13 nm uniform gamma-Fe_2O_3 particles dispersed in water and hexane. Although hexane allows the disagglomerated obtaining particle system; aggregation is observed in the case of water colloids. The zero field cooled (ZFC) curves show a discontinuity in the magnetization values associated with the melting points of water and hexane. Additionally, for 13 nm gamma-Fe_2O_3 dispersed in hexane, a second magnetization jump is observed that depends on particle concentration and shifts toward lower temperature by increasing applied field. This second jump is related to the strength of the magnetic interactions as it is only present in disagglomerated particle systems with the largest size, i.e., is not observed for 8 nm superparamagnetic particles, and surface effects can be discarded. The specific absorption rate (SAR) decreases with increasing concentration only for the hexane colloid, whereas for aqueous colloids, the SAR is almost independent of particle concentration. Our results suggest that, as a consequence of the magnetic interactions, the dipolar field acting on large particles increases with concentration, leading to a decrease of the SAR

Standardisation of magnetic nanoparticles in liquid suspension

Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation, spanning a large number of industry sectors from imaging and actuation based applications in biomedicine and biotechnology, through large-scale environmental remediation uses such as water purification, to engineering-based applications such as position-controlled lubricants and soaps. Continuous advances in their manufacture have produced an ever-growing range of products, each with their own unique properties. At the same time, the characterisation of magnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpret the measurement data. In many cases, the stringent requirements of the end-user technologies dictate that magnetic nanoparticle products should be clearly defined, well characterised, consistent and safe; or to put it another way—standardised. The aims of this document are to outline the concepts and terminology necessary for discussion of magnetic nanoparticles, to examine the current state-of-the-art in characterisation methods necessary for the most prominent applications of magnetic nanoparticle suspensions, to suggest a possible structure for the future development of standardisation within the field, and to identify areas and topics which deserve to be the focus of future work items. We discuss potential roadmaps for the future standardisation of this developing industry, and the likely challenges to be encountered along the way

Specific absorption rate dependence on temperature in magnetic field hyperthermia measured by dynamic hysteresis losses (ac magnetometry).

Magnetic nanoparticles (NPs) are intensively studied for their potential use for magnetic hyperthermia, a treatment that has passed a phase II clinical trial against severe brain cancer (glioblastoma) at the end of 2011. Their heating power, characterized by the 'specific absorption rate (SAR)', is often considered temperature independent in the literature, mainly because of the difficulties that arise from the measurement methodology. Using a dynamic magnetometer presented in a recent paper, we measure here the thermal dependence of SAR for superparamagnetic iron oxide (maghemite) NPs of four different size-ranges corresponding to mean diameters around 12 nm, 14 nm, 15 nm and 16 nm. The article reports a parametrical study extending from 10 to 60 °C in temperature, from 75 to 1031 kHz in frequency, and from 2 to 24 kA m(-1) in magnetic field strength. It was observed that SAR values of smaller NPs decrease with temperature whereas for the larger sample (16 nm) SAR values increase with temperature. The measured variation of SAR with temperature is frequency dependent. This behaviour is fully explained within the scope of linear response theory based on Néel and Brown relaxation processes, using independent magnetic measurements of the specific magnetization and the magnetic anisotropy constant. A good quantitative agreement between experimental values and theoretical values is confirmed in a tri-dimensional space that uses as coordinates the field strength, the frequency and the temperature.Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therap

Challenges and recommendations for magnetic hyperthermia characterization measurements

Purpose: The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields–a process known as magnetic field hyperthermia (MFH)–can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating–characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg–is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. Materials and Methods: An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing. Results: The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. Conclusion: We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology