Pericellular hydrogel/nanonets inhibit cancer cells.

Pericellular hydrogel/nanonets inhibit cancer cells.
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周围水凝胶/纳米蛋白抑制癌细胞。

DOI:
10.1002/anie.201402216
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发表时间:
2014-07-28
影响因子:
16.6
通讯作者:
Xu, Bing
Xu, Bing
中科院分区:
化学1区
文献类型:
--
作者:
Kuang, Yi;Shi, Junfeng;Li, Jie;Yuan, Dan;Alberti, Kyle A.;Xu, Qiaobing;Xu, Bing

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由蛋白质形成的原纤维是细胞的重要组成部分。然而,尚未观察到小分子异源纳米原纤维在哺乳动物细胞上的选择性形成。在这里,我们报告了细胞周间隙中小 D-肽衍生物的水凝胶/纳米网的意外观察。表面和分泌磷酸酶使水凝胶剂的前体去磷酸化,以触发水凝胶剂的自组装,并选择性地在过度表达磷酸酶的癌细胞周围产生细胞周水凝胶/纳米网。基于细胞的测定证实,细胞周水凝胶/纳米网会阻止细胞物质交换,从而诱导癌细胞凋亡,包括多药耐药(MDR)癌细胞MES-SA/Dx5。小分子的细胞周水凝胶/纳米网表现出独特的功能,说明了一种在细胞微环境中时空设计分子组装以抑制癌细胞生长甚至转移的全新方法。
Fibrils formed by proteins are vital components for cells. However, selective formation of xenogenous nanofibrils of small molecules on mammalian cells has yet to be observed. Here we report an unexpected observation of hydrogel/nanonets of a small D-peptide derivative in pericellular space. Surface and secretory phosphatases dephosphorylate a precursor of a hydrogelator to trigger the self-assembly of the hydrogelator and to result in pericellular hydrogel/nanonets selectively around the cancer cells that overexpress phosphatases. Cell based assays confirm that the pericellular hydrogel/nanonets block cellular mass exchange to induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5. Pericellular hydrogel/nanonets of small molecules to exhibit distinct functions illustrates a fundamentally new way to engineer molecular assemblies spatiotemporally in cellular microenvironment for inhibiting cancer cell growth and even metastasis.
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