3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho , Headquarters of the European Institute of Excellence in Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal.
J Am Chem Soc. 2015 Jan 21;137(2):576-9. doi: 10.1021/ja5111893. Epub 2015 Jan 8.
We report on a simple carbohydrate amphiphile able to self-assemble into nanofibers upon enzymatic dephosphorylation. The self-assembly can be triggered by alkaline phosphatase (ALP) in solution or in situ by the ALP produced by osteosarcoma cell line, SaOs2. In the latter case, assembly and localized gelation occurs mainly on the cell surface. The gelation of the pericellular environment induces a reduction of the SaOs2 metabolic activity at an initial stage (≤7 h) that results in cell death at longer exposure periods (≥24 h). We show that this effect depends on the phosphatase concentration, and thus, it is cell-selective with prechondrocytes ATDC5 (that express ∼15-20 times lower ALP activity compared to SaOs2) not being affected at concentrations ≤1 mM. These results demonstrate that simple carbohydrate derivatives can be used in an antiosteosarcoma strategy with limited impact on the surrounding healthy cells/tissues.
我们报告了一种简单的碳水化合物两亲物，它能够在酶去磷酸化时自组装成纳米纤维。自组装可以通过溶液中的碱性磷酸酶（ALP）或通过骨肉瘤细胞系 SaOs2 产生的 ALP 原位触发。在后一种情况下，组装和局部凝胶化主要发生在细胞表面。细胞外环境的凝胶化会导致 SaOs2 代谢活性在初始阶段（≤7 小时）降低，从而导致在较长暴露时间（≥24 小时）时细胞死亡。我们表明，这种效应取决于磷酸酶浓度，因此，它对 Prechondrocytes ATDC5 具有细胞选择性（与 SaOs2 相比，其 ALP 活性低约 15-20 倍），在浓度≤1 mM 时不受影响。这些结果表明，简单的碳水化合物衍生物可用于抗骨肉瘤策略，对周围健康细胞/组织的影响有限。
