Ectoenzyme switches the surface of magnetic nanoparticles for selective binding of cancer cells.
Ectoenzyme switches the surface of magnetic nanoparticles for selective binding of cancer cells.
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DOI：
10.1016/j.jcis.2014.12.023
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发表时间：
2015-06-01
影响因子：
9.9
通讯作者：
Xu, Bing
中科院分区：
文献类型：
--
作者：
Du, Xuewen;Zhou, Jie;Xu, Bing
蛋白质的磷酸化和去磷酸化等酶开关是细胞信号转导的最重要机制。受自然的启发和我们最近意外地观察到D-酪氨酸磷酸小肽的去磷酸化，我们用D-酪氨酸磷酸修饰磁性纳米颗粒(MNP)的表面，这是碱性磷酸酶(ALP)的底物。我们的研究发现，碱性磷酸酶能够去除磁性纳米颗粒中的磷酸基团。最重要的是，胎盘碱性磷酸酶(ALPP)是一种胞外酶，位于细胞表面，具有质膜外的催化结构域，在许多癌细胞上过表达，它能使磁性纳米颗粒表面的D-酪氨酸磷酸酯去磷酸化，使磁性纳米颗粒选择性地附着在癌细胞上，如HeLa细胞。与常用抗体不同，磁性纳米颗粒对癌细胞的选择性来自于ALPP催化的酶反应。利用酶反应来调节各种纳米结构的表面可能会导致一种通用的方法来广泛地靶向癌细胞，而不依赖于特定的配体-受体相互作用(例如抗体)。因此，这项工作展示了一种全新的概念，允许细胞主动设计胶体材料的表面，如磁性纳米颗粒，用于各种应用。
Enzymatic switch, such as phosphorylation and dephosphorylation of proteins, is the most important mechanism for cellular signal transductions. Inspired by Nature and encouraged by our recent unexpected observation of the dephosphorylation of D-tyrosine phosphate-contain small peptides, we modify the surface of magnetic nanoparticles (MNP) with D-tyrosine phosphate that is a substrate of alkaline phosphatase (ALP). Our studies find that ALP is able to remove the phosphate groups from the magnetic nanoparticles. Most importantly, placental alkaline phosphatase (ALPP), an ectoenzyme that locates on cell surface with catalytic domains outside the plasma membrane and is overexpressed on many cancer cells, dephosphorylate the D-tyrosine phosphates on the surface of the magnetic nanoparticle and enable the magnetic nanoparticles to adhere selectively to the cancer cells, such as HeLa cells. Unlikely commonly used antibodies, the selectivity of the magnetic nanoparticles to cancer cells originates from the enzymatic reaction catalyzed by ALPP. The use of enzymatic reaction to modulate the surface of various nanostructures may lead to a general method to broadly target cancer cells without relying on specific ligand-receptor interactions (e.g., antibodies). This work, thus, illustrates a fundamentally new concept to allow cells to actively engineer the surface of colloids materials, such as magnetic nanoparticles, for various applications.
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影响因子：
8.4
作者：
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通讯作者：
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通讯作者：
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