Controlling Cancer Cell Fate Using Localized Biocatalytic Self-Assembly of an Aromatic Carbohydrate Amphiphile
Controlling Cancer Cell Fate Using Localized Biocatalytic Self-Assembly of an Aromatic Carbohydrate Amphiphile
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DOI：
10.1021/ja5111893
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发表时间：
2015-01-21
影响因子：
15
通讯作者：
Pashkuleva, Iva
中科院分区：
文献类型：
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作者：
Pires, Ricardo A.;Abul-Haija, Yousef M.;Pashkuleva, Iva
我们报道了一种简单的碳水化合物两亲体，能够在酶解磷酸化后自组装成纳米纤维。这种自组装可以由碱性磷酸酶（ALP）在溶液中触发，也可以由骨肉瘤细胞系SaOs2产生的ALP在原位触发。在后一种情况下，组装和局部凝胶化主要发生在细胞表面。细胞周围环境的凝胶化在初始阶段（= 24 h）诱导SaOs2代谢活性降低。我们发现这种作用取决于磷酸酶的浓度，因此，它是细胞选择性的，软骨前细胞ATDC5（与SaOs2相比，其表达的ALP活性低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以用于抗骨肉瘤策略，对周围健康细胞/组织的影响有限。
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 (= 24 h). We show that this effect depends on the phosphatase concentration, and thus, it is cell-selective with prechondrocytes ATDC5 (that express similar to 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.