GIP ARRONAX, 1 rue Aronnax, CS 10112, F-44817 Nantes, CEDEX 3, France.
SUBATECH, 4 rue Alfred Kastler, BP 20722, F-44307 Nantes, CEDEX 3, France.
Molecules. 2021 Feb 20;26(4):1143. doi: 10.3390/molecules26041143.
(1) Background: Exopolysaccharide (EPS) derivatives, produced by bacterium, showed anti-metastatic properties. They may represent a new class of ligands to be combined with theranostic radionuclides, such as Sc/Sc. The goal of this work was to investigate the feasibility of such coupling. (2) Methods: EPSs, as well as heparin used as a drug reference, were characterized in terms of molar mass and dispersity using Asymmetrical Flow Field-Flow Fractionation coupled to Multi-Angle Light Scattering (AF4-MALS). The intrinsic viscosity of EPSs at different ionic strengths were measured in order to establish the conformation. To determine the stability constants of Sc with EPS and heparin, a Free-ion selective radiotracer extraction (FISRE) method has been used. (3) Results: AF4-MALS showed that radical depolymerization produces monodisperse EPSs, suitable for therapeutic use. EPS conformation exhibited a lower hydrodynamic volume for the highest ionic strengths. The resulting random-coiled conformation could affect the complexation with metal for high concentration. The Log of Sc-EPS complexes have been determined and showing that they are comparable to the Sc-Hep. (4) Conclusions: EPSs are very promising to be coupled with the theranostic pair of scandium for Nuclear Medicine.
(1) 背景:细菌产生的胞外多糖 (EPS) 衍生物具有抗转移特性。它们可能代表一类与治疗性放射性核素(如 Sc/Sc)结合的新型配体。这项工作的目的是研究这种偶联的可行性。
(2) 方法:采用不对称流场流分离-多角度光散射联用技术(AF4-MALS)对 EPS 以及用作药物对照的肝素进行摩尔质量和分散度的表征。测量了 EPS 在不同离子强度下的特性粘度,以确定其构象。为了确定 Sc 与 EPS 和肝素的稳定常数,采用了游离离子选择放射性示踪萃取(FISRE)法。
(3) 结果:AF4-MALS 表明,自由基解聚产生的单分散 EPS 适用于治疗用途。对于最高的离子强度,EPS 构象表现出较低的流体力学体积。所得的无规卷曲构象可能会影响高浓度下与金属的络合。已经确定了 Sc-EPS 配合物的对数,表明它们与 Sc-Hep 相当。
(4) 结论:EPS 非常有希望与放射性核素 Sc 偶联用于核医学的治疗。