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

Inversion of the horizontal-to-vertical spectral ratio in presence of strong lateral heterogeneity

The horizontal-to-vertical spectral ratio (HVSR) method has recently gained a resurgence of interest because of its new interpretation through the diffuse field approach. According to this theory, the HVSR measurement is linked to the Green's function retrieval. While the HVSR method is traditionally used to evaluate simple and shallow velocity model, we demonstrate that complex Earth' structure (that includes composite geological layering) can be assessed by choosing appropriate data processing and inversion scheme. In particular, we explore the effects of a strong lateral heterogeneity on the HVSR by using measurements along a vertical crater wall. However, wave propagation computation with lateral heterogeneity is inefficient to conduct an inversion. Then, to accelerate the forward calculation, we identified a simplified model consisting of an unbounded 2-D multilayer medium that allows describing the observed measurements with the use of a correction factor. The 2-D character comes from a nonstandard noise illumination related to the wind blowing perpendicularly to the crater walls. It is supported by several theoretical and experimental arguments. We also show that the H and V components can be retrieved independently, which may improve the sensitivity of the inversion at high frequency. To reduce the non-uniqueness of the problem, we consider the joint inversion of the H and HVSR's at several positions where the thicknesses of the layers were evaluated thanks to a large geological outcrop. The good agreement between the recovered velocity structure and the geology shows that the method is not limited to unbounded simple shallow structures, which opens the domains of application of the method to exploration geophysics or to hazard assessment

Diffraction of picosecond bulk longitudinal and shear waves in micron thick films

Investigation of thin metallic film properties by means of picosecond ultrasonics [C. Thomsen et al., Phys. Rev. Lett. 53, 989 (1984)] has been under the scope of several studies. Generation of longitudinal and shear waves [T. Pézeril et al., Phys. Rev. B 73, 132301 (2006); O. Matsuda et al., Phys. Rev. Lett. 93, 095501 (2004)] with a wave vector normal to the film free surface has been demonstrated. Such measurements cannot provide complete information about properties of anisotropic films. Extreme focusing of a laser pump beam (≈0.5 μm) on the sample surface has recently allowed us to provide evidence of picosecond acoustic diffraction in thin metallic films (≈1 μm) [C. Rossignol et al., Phys. Rev. Lett. 94, 166106 (2005)]. The resulting longitudinal and shear wavefronts propagate at group velocity through the bulk of the film. To interpret the received signals, source directivity diagrams are calculated taking into account material anisotropy, optical penetration, and laser beam width on the sample surface. It is shown that acoustic diffraction increases with optical penetration, so competing with the increasing of directivity caused by beam width. Reflection with mode conversion at the film-substrate interface is discussed

Developments in signal processing and interpretation in laser tapping

A novel technique, called laser-tapping, based on the thermoelastic excitation by laser like laser-ultrasonics has been previously introduced for inspecting honeycomb and foam core structures. If the top skin is delaminated or detached from the substrate, the detached layer is driven into vibration. The interpretation of the vibrations in terms of Lamb wave resonances is first discussed for a flat bottom hole configuration and then used to determine appropriate signal processing for samples such as honeycomb structures.Peer reviewed: YesNRC publication: Ye

Bonding quality detection of composite structure by laser shock wave

The carbon fiber reinforced polymer (CFRP) is more and more attractive because of its excellent mechanical performances, while the application of CFRP is limited because the non-destructive evaluation method is still not well done. A method based on shock waves produced by a pulsed laser is applied to the evaluation of bond quality of CFRP plates joined by an adhesive layer. A laser shock wave can cause a tension when it propagates through the adhesive/plate interface. A good bond will be unaffected by a certain level of shock wave stress whereas a weaker one will be damaged. In the experiments, the sample surface velocities are optically measured with an interferometer. The signals give a signature of well-bond or bad ones, and are used to obtain an estimate of the bond strength. Results show that the proposed test is able to differentiate bond quality. Laser-ultrasonic measurements made on shocked samples also confirm that weak bonds are revealed by the laser shock wave. The development of this technique will probably make the on line evaluation of CFRP structure possible in the future.Peer reviewed: YesNRC publication: Ye

Generation and detection of shear acoustic waves in metal submicrometric films with ultrashort laser pulses

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Femtosecond laser generation and detection of longitudinal and shear acoustic waves in a sub-micrometric film

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