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用含有苯硼酸的聚合物刷修饰的双响应表面,可实现对癌细胞的可逆捕获和释放。

Dual-responsive surfaces modified with phenylboronic acid-containing polymer brush to reversibly capture and release cancer cells.

机构信息

Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

出版信息

J Am Chem Soc. 2013 May 22;135(20):7603-9. doi: 10.1021/ja401000m. Epub 2013 May 8.

Abstract

Artificial stimuli-responsive surfaces that can mimic the dynamic function of living systems have attracted much attention. However, there exist few artificial systems capable of responding to dual- or multistimulation as the natural system does. Herein, we synthesize a pH and glucose dual-responsive surface by grafting poly(acrylamidophenylboronic acid) (polyAAPBA) brush from aligned silicon nanowire (SiNW) array. The as-prepared surface can reversibly capture and release targeted cancer cells by precisely controlling pH and glucose concentration, exhibiting dual-responsive AND logic. In the presence of 70 mM glucose, the surface is pH responsive, which can vary from a cell-adhesive state to a cell-repulsive state by changing the pH from 6.8 to 7.8. While keeping the pH at 7.8, the surface becomes glucose responsive--capturing cells in the absence of glucose and releasing cells by adding 70 mM glucose. Through simultaneously changing the pH and glucose concentration from pH 6.8/0 mM glucose to pH 7.8/70 mM glucose, the surface is dual responsive with the capability to switch between cell capture and release for at least 5 cycles. The cell capture and release process on this dual-responsive surface is noninvasive with cell viability higher than 95%. Moreover, topographical interaction between the aligned SiNW array and cell protrusions greatly amplifies the responsiveness and accelerates the response rate of the dual-responsive surface between cell capture and release. The responsive mechanism of the dual-responsive surface is systematically studied using a quartz crystal microbalance, which shows that the competitive binding between polyAAPBA/sialic acid and polyAAPBA/glucose contributes to the dual response. Such dual-responsive surface can significantly impact biomedical and biological applications including cell-based diagnostics, in vivo drug delivery, etc.

摘要

人工刺激响应表面可以模拟生命系统的动态功能,因此受到了广泛关注。然而,能够像自然系统那样对双或多刺激做出响应的人工系统还很少。在此,我们通过从取向硅纳米线(SiNW)阵列上接枝聚(丙烯酰胺基苯硼酸)(polyAAPBA)刷,合成了一种 pH 和葡萄糖双响应表面。通过精确控制 pH 值和葡萄糖浓度,该表面可以可逆地捕获和释放靶向癌细胞,表现出双响应 AND 逻辑。在 70mM 葡萄糖存在的情况下,表面呈 pH 响应性,通过将 pH 值从 6.8 改变到 7.8,可以使表面从细胞黏附状态变为细胞排斥状态。保持 pH 值为 7.8 时,表面变为葡萄糖响应性--在没有葡萄糖的情况下捕获细胞,并通过添加 70mM 葡萄糖释放细胞。通过同时将 pH 值和葡萄糖浓度从 pH 6.8/0mM 葡萄糖改变为 pH 7.8/70mM 葡萄糖,该表面具有双响应性,能够在细胞捕获和释放之间进行至少 5 次切换。双响应表面上的细胞捕获和释放过程是非侵入性的,细胞活力高于 95%。此外,取向 SiNW 阵列和细胞突起之间的形貌相互作用极大地增强了双响应表面在细胞捕获和释放之间的响应性,并加速了其响应速率。通过石英晶体微天平系统地研究了双响应表面的响应机制,表明 polyAAPBA/唾液酸和 polyAAPBA/葡萄糖之间的竞争结合有助于双响应。这种双响应表面可以显著影响包括基于细胞的诊断、体内药物输送等在内的生物医学和生物学应用。

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