Marine Le Goas, Tom Roussel, Maria Kalbazova, David Carrière, Elodie Barruet, Valerie Geertsen, Giulia C. Fadda, Fabienne Testard, Geraldine Carrot and Jean-Philippe Renault

Nanomedicines are considered as promising therapeutics for cancer treatment. However, clinical translation is still scarce, partly because their biological behavior is not well understood. Extracting general guidelines from the great variety of nanoparticles and conditions studied is indeed difficult, and relevant techniques are lacking to obtain in situ information. Here, both issues are solved by combining versatile model nanoparticles with in situ tools based on small-angle scattering techniques (SAS). The strategy was to develop a library of nanoparticles and perform systematic study of their interactions with biological systems. Considering the promising properties of gold nanoparticles as cancer therapeutics, polymethacrylate-grafted gold nanoparticles were chosen as models. Modulation of polymer chemistry was shown to change the surface properties while keeping the same structure for all nanoparticles. This unity allowed reliable comparison to extract general principles, while the synthesis versatility enabled to fine-tune the nanoparticles surface properties, especially through copolymerization, and thus to optimize their biological behavior. Two specific aspects were particularly examined: colloidal stability and cell uptake. Positive charges and hydrophobicity were identified as key parameters influencing toxicity and internalization. In situ SAS gave valuable information about nanoparticles evolution in biologically relevant environments. Good colloidal stability was thereby shown in cell culture media, while intracellular transformation and quantity of nanoparticles were monitored, highlighting the potential of these techniques for nanomedicines studies.

https://doi.org/10.1039/d0tb01167c

¹ Max-Planck-Institut für Festkörperforschung, Heisenbergstraße 1, 70569 Stuttgart, Germany
² Laboratoire Léon Brillouin, CEA-CNRS, CEA Saclay, 91191 Gif-sur-Yvette, France
³ Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM-II), TU München, D-85747 Garching, Germany

In March 2008, superconductivity at high critical temperature (Tc> 50K) was found in iron-arsenide compounds  [1] to the surprise of the scientific community. Indeed, the magnetic iron was rather regarded as an antagonist of superconductivity. Moreover, it is the first time that a so high critical temperature is reached without copper. Very like copper oxide superconductors, these new superconductors have a lamellar structure with layers of iron and "pnictures" (compounds of As, P. .., that are elements of the 15th column of the Mendeleyev table) which are interposed between plans of "charge reservoirs" (see figure). These materials also present a phase diagram similar to that of cuprates with, versus the doping concentration, an antiferromagnetic phase adjacent to the superconducting zone ( [2]).

The mechanical properties of boron carbide at high pressure, explained from first principles.

By theoretical methods based on the density functional theory (DFT and DFPT) [1] [2], the physical properties of boron carbide have been studied for different carbon concentrations and versus temperature and pressure. A type of defect is identified, whose appearance at high pressure and high temperature, can explain the poor mechanical strength upon impact of the material . These results point the way to synthesize a superconducting material combining good mechanical strength at high pressure.

Liquid-state NMR is a very powerful method for chemical analysis but it suffers from inherent low sensitivity due to the weak involved energies, which leads to small thermal equilibrium polarization. A solution consists in resorting to transiently polarized nuclear spin systems such as those prepared by optical pumping or dynamic nuclear polarization. Nevertheless, the direct extension of the whole liquid-state NMR techniques to these systems might be less straightforward than anticipated. Indeed their nuclear magnetization can easily be on the same order of magnitude or much larger than that of bulk water in high field. For such high magnetization levels, the usual framework of NMR fails to describe the collective spin dynamics which appears [1]. It originates from the non-linear coupling between the magnetization and the detecting coil (radiation damping) and from the massive long distance dipolar couplings between the nuclear spins.

In this field, we have observed and characterized a new and unexpected phenomenon. The magnetization of dissolved hyperpolarized ¹²⁹Xe is first prepared in its unstable state (negative xenon spin temperature) by the optical pumping process. When put in the high field NMR magnet, without rf excitation, the system spontaneously emits a series of rf bursts instead of one, as expected by the usual theory of radiation damping. We have experimentally shown that this also induces inhomogeneous spatial organization of the ¹²⁹Xe magnetization. Even if it appears possible, by numerical simulations, to reproduce one emission leading to inhomogeneous spatial magnetization, a series seems to be impossible to obtain in the framework of a classical dipolar field. We have been able to prove that these multiple maser emissions are triggered by noise but the origin of the chaos remains unclear. Even if many elements indicate the main influence of long distance dipolar fields, in particular through the appearance of frequency beats or of very narrow lines, the chaos might also be due to the non-linearity of the Bloch-Maxwell equations as in chaotic laser at quasi-optical wave lengths.

A practical technical consequence of this research was the finding of a new tuning approach which allows an increase of NMR sensitivity valid for any nuclear spin system [3].

This work is supported by the French Ministry of research, ANR Blanche DIPOL).

[1] J. Jeener, in Encyclopedia of NMR, 9 (Eds.: D. M. Grant, R. K. Harris), Wiley, (2002), pp. 642-679.

[2] D. J. Marion, G. Huber, P. Berthault, H. Desvaux, ChemPhysChem, 9, 1395-1401 (2008).

(3] D. J. Marion, H. Desvaux, J. Magn. Reson., 193, 153-157 (2008).