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

Universität Heidelberg IWR INF 368

We compare several definitions of the Galois group of a linear difference equation that have arisen in algebra, analysis and model theory and show, that these groups are isomorphic over suitable fields. In addition, we study properties of Picard-Vessiot extensions over fields with not necessarily algebraically closed subfields of constants.

Difference Galois theory of linear differential equations

International audienc

Bulk Immiscibility at the Edge of the Nanoscale

In the quest to identify more effective catalyst nanoparticles for many industrially important applications, the Au–Pt system has gathered considerable attention. Despite considerable effort the interplay between phase equilibrium behavior and surface segregation in Au–Pt nanoparticles is still poorly understood. Here we investigate the phase equilibrium behavior of 20 nm Au–Pt nanoparticles using a combination of high-resolution scanning transmission electron microscopy and a hybrid Monte Carlo and molecular dynamics atomistic simulation technique. Our approach takes into account the effects of immiscibility, elastic strain, interfacial free energy, and surface segregation. This is used to explain two key phenomena taking place in these nanoparticles. The first is whether the binary system remains immiscible at the nanoscale, and if so what morphology would the secondary phase take. Our findings suggest that even at sizes of 20 nm, thermally equilibrated Au–Pt nanoparticles remain largely immiscible and behave thermodynamically as bulk-like systems. We explain why 20 nm Au–Pt nanoparticles phase separate into hemispheres as opposed to a thick-shelled core–shell structure. These insights are central to further optimization of Au–Pt nanoparticles toward enhanced catalytic activities. The phase-separated Janus particles observed in this study offer enhanced material functionality arising from the nonuniformity of their plasmonic, catalytic, and surface properties

Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: A synthesis of genetic association studies

Background: Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results. Materials and methods: In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta-analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (ORG). Cumulative and recursive cumulative meta-analyses were also performed. Results: The analysis showed marginal significant association for the C677T variant, overall [OR = 0.91 (0.82-1.00) and ORG = 0.89 (0.79-1.01)], and in Whites [OR = 0.88 (0.77-0.99) and ORG = 0.85 (0.73-0.99)]. The A1298C variant produced non-significant results. For both variants, the cumulative meta-analysis did not show a trend of association as evidence accumulates and the recursive cumulative meta-analysis indicated lack of sufficient evidence for denying or claiming an association. Conclusion: The current evidence is not sufficient to draw definite conclusions regarding the association of MTHFR variants and development of ALL. (C) 2011 Elsevier Ltd. All rights reserved