Evaluation of polysaccharides for bone oncology applications30m
M.Mazzaa,b, C. Alliota,c, C. Sinquind, P.E. Reillerce, S. Colliec-Jouaultd, and S. Huclier-Markaia,b*
a GIP ARRONAX, 1 rue Arronax, F-44817 Nantes Cedex 3, France.
b SUBATECH, 4 rue Alfred Kastler, BP 20722, 44307 Nantes Cedex 3, France
c INSERM U892- 8 quai Moncousu, F-44007 Nantes Cedex 1, France.
d IFREMER, Institut français de recherche pour l’exploitation de la mer, rue de l’Ile d’Yeu, BP 21105 F-44311 Nantes Cedex 3, France.
e Den – Service d’Etudes Analytiques et de Réactivité des Surfaces (SEARS), CEA, Université Paris-Saclay, F-91191, Gif sur Yvette, France.
An oversulphated exopolysaccharide (OS-EPS) derivative, produced by a deep-sea hydrothermal bacterium named Alteromonas infernus, has shown to inhibit the establishment of lung metastasis in patients with osteosarcoma. These EPSs have anticoagulant properties that could reduce the thrombotic complication affecting some kind of tumors. Heparin is currently used in therapy for that purpose, but with the risk of prion, that is not the case of polysaccharides. Thus, this new class of molecules could pave the way to new type of applications in oncology and the idea of this work is to investigate the coupling of these EPS with a theranostic radionuclide pair, such as 44Sc/47Sc.
A very important part of this work is dedicated to an extensive characterization of these very complexe molecules to be further used for medical purposes. EPSs have been characterized in terms of molecular weight and dispersity using High Performance Size Exclusion Chromatography (HPSEC) coupled to Multi Angle Light Scattering (MALS) as well as Asymmetrical Flow Field-Flow Fractionation (A4F) coupled to MALS. A4F-MALS showed that EPSs are monodisperse polysaccharides with a polydispersity index (IP) of 1.4, suitable for therapeutic uses.
To have an idea on the conformation of these polymers in solution, the intrinsic viscosity for EPS and heparin as reference, has been measured at different ionic strength of solvent revealing that polymer conformation could become more folded increasing the added salt. The conformation may lay an important role then on the biodistribution of these molecules in vivo.
Finally, the stability constants of Sc-EPS complexes must be determined. We have based our approach on two techniques: potentiometric titrations and time-resolved laser fluorescence spectroscopy (TRLFS). TRLFS requires a fluorescent probe, such as Eu3+ which has also a coordination chemistry close to Sc3+. Moreover, TRLFS allows to measure stability constants only using traces of EPS, avoiding wastes and chemical degradation compared to titrations. Potentiometric titrations are not suitable for such complex systems, but this method was employed on purpose for the determination of the pKa of heparin (3,65) and the number of heparin dimers (33). Work is still on-going for Sc/Eu-EPS systems.
The corresponding half-life T =(1.8 ±0.5(stat) ± 0.1 (syst))x10^22 y is longest ever measured directly.
XENON1T, a dark matter detection experiment for the neutrino physics30m
XENON1T is the third experiment of the XENON collaboration. Project realized for dark matter direct detection, it consists of a dual-phase (liquid-gas) time projection chamber (TPC) filled with xenon. With its total mass of 3.2 tonnes of xenon, XENON1T is the largest TPC ever built for dark matter searches. It proved to be capable to reach the lowest background level ever achieved in liquid xenon detector.
Conceived to detect elastic scattering of Weakly Interactive Massive Particles (WIMPs) with the target nuclei (that induce a low energy nuclear recoils, below 100 keV), XENON1T set the world best limit on the spin-independent nucleus-WIMP cross-section, with a minimum at 4.1x10-47cm2 for a WIMP mass of 30 GeV/c2 at 90% confidence level.
Thanks to the ultra-low background environment, the same detector allows to study other rare processes. Among them, the search for neutrinoless double ß decay, meant to probe the majorana nature of neutrinos, is ongoing. This search is possible thanks the natural presence of the 136Xe double ß decay isotope. The signal expected is an electronic recoil at higher energy (~2.6 MeV) with respect to dark matter searches.
A dedicated analysis to study this energy region is required and will be introduced in this presentation.