Challenges and Recommendations for Magnetic Hyperthermia Characterization Measurements

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 nHm2/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. To address this, we report here on 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. 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. 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.Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therap

Whither magnetic hyperthermia? A tentative roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia

Whither Magnetic Hyperthermia? A Tentative Roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02)

Unveiling the role of surface, size, shape and defects of iron oxide nanoparticles for theranostic applications

Iron oxide nanoparticles (IONPs) are well-known contrast agents for MRI for a wide range of sizes and shapes. Their use as theranostic agents requires a better understanding of their magnetic hyperthermia properties and also the design of a biocompatible coating ensuring their stealth and a good biodistribution to allow targeting of specific diseases. Here, biocompatible IONPs of two different shapes (spherical and octopod) were designed and tested in vitro and in vivo to evaluate their abilities as high-end theranostic agents. IONPs featured a dendron coating that was shown to provide anti-fouling properties and a small hydrodynamic size favoring an in vivo circulation of the dendronized IONPs. While dendronized nanospheres of about 22 nm size revealed good combined theranostic properties (r2 = 303 mM s−1, SAR = 395 W gFe−1), octopods with a mean size of 18 nm displayed unprecedented characteristics to simultaneously act as MRI contrast agents and magnetic hyperthermia agents (r2 = 405 mM s−1, SAR = 950 W gFe−1). The extensive structural and magnetic characterization of the two dendronized IONPs reveals clear shape, surface and defect effects explaining their high performance. The octopods seem to induce unusual surface effects evidenced by different characterization techniques while the nanospheres show high internal defects favoring Néel relaxation for magnetic hyperthermia. The study of octopods with different sizes showed that Néel relaxation dominates at sizes below 20 nm while the Brownian one occurs at higher sizes. In vitro experiments demonstrated that the magnetic heating capability of octopods occurs especially at low frequencies. The coupling of a small amount of glucose on dendronized octopods succeeded in internalizing them and showing an effect of MH on tumor growth. All measurements evidenced a particular signature of octopods, which is attributed to higher anisotropy, surface effects and/or magnetic field inhomogeneity induced by tips. This approach aiming at an analysis of the structure–property relationships is important to design efficient theranostic nanoparticles.The Region Alsace, France, and the Labex Chimie des Systemes Complexes, University of Strasbourg, France are gratefully acknowledged for the doctoral fellowship to Geoffrey Cotin. This research project was also co-funded by Labex CSC, Alsace contre le cancer, INCA (project PRTK14, THERAMAG 2014-225) and the INTERREG project NANOTRANSMED. The “NANOTRANSMED” project is co-funded by the European Regional Development Fund (ERDF) and by the Swiss Confederation and the Swiss cantons of Aargau, Basel-Landschaft and Basel-Stadt, in the framework of the INTERREG V Upper Rhine program (“Transcending borders with every project”). The authors thank Morgane Rabineau for epifluorescence imaging and Nadia Messaddeq for TEM imaging of cells. The authors thank the Center for Microscopy and Molecular Imaging (CMMI, supported by the European Regional Development Fund and the Walloon Region). This work was supported by the Fond National de la Recherche Scientifique (FNRS), UIAP VII, ARC Programs of the French Community of Belgium and the Walloon region (Gadolymph and Holocancer programs). All the authors acknowledge the COST action TD1402 “RADIOMAG”. D. Ortega and F. J. Teran acknowledge support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686), the Spanish Ministry of Economy and Competitiveness for the NANOLICO project (MAT2017-85617-R), the Spanish Ministry of Science through the NaNoCAR grant PID2020-117544RB-I00, the Ramón y Cajal grant RYC2018-025253-I and Research Networks grant RED2018-102626-T, the HEATOOLS project (BIO2017-84246-C2-1-R), the Comunidad de Madrid for grant NANOMAGCOST (P2018/NMT-4321), DGA for public funding from Fondo Social (grupos DGA), and the European Commission for the funding received through the H2020 “NoCanTher” project (GA No. 685795).Peer reviewe

Detrital magnetizations from redeposition experiments of different natural sediments

International audienceWe carried out several experiments with carbonate-rich and clay-rich sediments that were redeposited in plastic cubes or in 1-meter-long cylindrical tubes with the aim of investigating the sensitivity of the depositional remanent magnetization (DRM) to various environmental and physical parameters. In contrast to previous studies, we did not observe any difference in the DRM acquired with or without saline water for either kind of sediment. Taking advantage of a gelatin that fixes the position of particles in suspension, we were able to measure the magnetization of suspended sediments within water-filled columns and thus to test the degree of alignment of magnetic grains. The magnetization of clay-rich sediments was not far from saturation but the magnetization was considerably reduced after deflocculation because the large flocs that favored alignment of magnetic grains were destroyed by the deflocculant. Similarly, the large flocs found at the bottom of the deposition tubes also reveal an efficient magnetic alignment. In contrast, the weak magnetization of the carbonate-rich sediments with small flocs yielded accurate and well-grouped magnetization directions that were not sensitive to deflocculation. Only a fraction of magnetic grains was mechanically oriented by the field in this case because of the weak net magnetic moments of the grains embedded within small flocs. The DRM was constrained by redeposition in plastic cubes performed without gelatin and with different field intensities. The DRM intensity of the carbonate-rich sediments is linearly related to field strength, which attests to their suitability for studies of relative paleointensity. Tests performed with mud from several stratigraphic levels in different marine sediment cores failed to reveal a significant influence of carbonate content on DRM, which suggests a relatively minor role of lithological changes on records of relative paleointensity

Magnetic susceptibility records for global stratigraphic correlations? New constraint in the context of carbonate platform reconstruction (Middle Devonian, Ardennes)

peer reviewedThis study undertakes a multi-disciplinary approach (sedimentology, magnetic susceptibility, geochemistry and hysteresis magnetic measurement) to increase our understanding of the Ardennes Givetian platform (Belgium and France) and to address a major question on the reliability of the magnetic susceptibility (MS) records for global correlations of marine carbonate records. Sedimentological analyses on two successions lasting millions of years, reveal an extended diversity of shallow- to off-reef palaeoenvironmental settings across the platform and allow to constrain the main sea-level fluctuations and associated environmental changes throughout the Givetian in Ardennes. The comparison of the two MS profiles allows to provide correlations, despite the long distance between the sections and their different sedimentological background. However, the comparison of the MS profiles from the Ardennes with contemporaneous data from the Rhenische Schiefergebirge (Germany) does not show any evidences of correlation, challenging studies that present the MS signal as a global correlation tool. These outcomes are crucial because they have repercussions on future global and regional stratigraphic issues as well as for paleoclimatic reconstructions. Here, we provide new evidences outlining that autogenic processes, which operate at long time scale, modulate the MS signal and have a strong influence over the magnetic susceptibility records that can leads to the absence of correlation within long-term MS trends

Stratigraphic correlations in mid- to late-Proterozoic carbonates of the Democratic Republic of Congo using magnetic susceptibility

In this paper, we have tested the application of magnetic susceptibility measurements in Cu-Ag-Zn-Pb-(Fe)-mineralized carbonates of the BIe subgroup (Democratic Republic of Congo) as an efficient tool for regional and global high-resolution stratigraphic correlations in the Neoproterozoic marine carbonates. To achieve this goal, we integrate the low-field magnetic susceptibility (XLF) data with facies analyses, geochemistry and isotope stratigraphy. The microfacies analyses of two cores, TshinyamaS70 and Kafuku15, drilled in the early Neoproterozoic carbonates of the Mbuji-Mayi Supergroup reveal a deep carbonate ramp setting associated with a microbial/stromatolitic mid-ramp environment. High-resolution stratigraphic correlations using magnetic susceptibility and C-isotope curves established for both cores, 190 km apart, suggest a sedimentary hiatus at the base of the TshinyamaS70 succession. C-O and Sr isotopes and Sr/Ca and Fe abundances show that a diagenetic meteoric overprint affected the series of the TshinyamaS70 core and a thermal effect related to mineralizing fluids affected the KafukuSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Influence of Atomic Doping on Thermal Stability of Ferrite Nanoparticles—Structural and Magnetic Studies

In this paper, a series of experiments are reported where ferrite nanoparticles were synthesized with different substitution percentages (5, 10, 15, or 20%) of Fe2+ by Co2+, Mn2+, or Ni2+ ions. Afterwards, the prepared nanoparticles were thermally treated between 50 and 500 °C in air for 24 h in order to observe how doping influences the oxidation process induced by temperature elevation and access to O2. Nanoparticles were imaged before and after thermal treatment by transmission electron microscopy and were analyzed by X-ray diffraction, vibrating sample magnetometry, and Mössbauer spectroscopy. Presented studies reveal that the amount and kind of doped transition metals (of replaced Fe2+) strongly affect the oxidation process of ferrite nanoparticles, which can govern the application possibility. Each transition element suppresses the oxidation process in comparison to pure Fe-oxides, with the highest impact seen with Ni2+