Institut de Cancérologie de l'Ouest, Université de Nantes, Blvd Jacques Monod, F-44805 Saint-Herblain, France.
GIP ARRONAX, 1 rue Aronnax, CEDEX 3, F-44817 Nantes, France.
Mar Drugs. 2021 Mar 23;19(3):174. doi: 10.3390/md19030174.
Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium Sc/Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.
已证实，细菌产生的胞外多糖 (EPS) 衍生物对鼠源和人源骨肉瘤细胞系 (POS-1 和 KHOS) 具有抗转移作用。这些衍生物对细胞周期没有显著影响，也没有对骨肉瘤细胞产生促凋亡作用。基于这一观察结果，这些 EPS 可以用作治疗用途的新型药物递送系统。治疗方法，即预测生物标志物与治疗剂的结合，已经得到了发展，特别是通过与真正的治疗性放射性核素对（如钪 Sc/Sc）结合来实现。然而，至关重要的是要确保一旦完成络合，载体的生物学特性保持完整，允许配体的分子亲向性识别其分子靶标。重要的是要评估当钪与聚合物络合时，在骨肉瘤细胞系上证明的 EPS 的生物学特性是否仍然存在，并将其扩展到其他癌细胞类型。因此，在体外测试了钪-EPS 复合物在人细胞系上的作用：MNNG/HOS 骨肉瘤、A375 黑色素瘤、A549 肺腺癌、U251 神经胶质瘤、MDA231 乳腺癌和 Caco2 结肠癌。使用 xCELLigence 实时细胞时间分析 (RTCA) 技术测定来监测不同细胞系 160 小时的增殖动力学。测试的复合物表现出抗增殖作用，这种作用比单独的 EPS 更有效。这种抗增殖特性的增加是由于 EPS 复合物的构象变化引起的，这种构象变化是由于其聚电解质性质在络合过程中诱导的。生长因子-受体信号和跨膜蛋白相互作用的改变可能是抗增殖作用的主要原因。这些结果非常有前景，表明 EPS 可以与钪结合以提高其生物学效应，并暗示配体没有发生主要的结构修饰。
