Biocompatible carbon nanotubes generated by functionalization with glycodendrimers
Biocompatible carbon nanotubes generated by functionalization with glycodendrimers
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DOI：
10.1002/anie.200705363
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Bertozzi, Carolyn R.
中科院分区：
文献类型：
--
作者：
Wu, Peng;Chen, Xing;Bertozzi, Carolyn R.
单壁碳纳米管（SWNTs）的结构、机械、电学和光学性质在其生物学应用中引起了人们极大的兴趣。[1-3]单壁碳纳米管已被用于生物传感，[4]成像，[5]细胞内递送，[6]和癌细胞靶向。[7，8]然而，在生命系统中扩大使用SWNT将需要减少其细胞毒性的策略。[9-12]因此，减轻SWNT毒性同时使特异性生物识别成为可能的表面改性是非常受欢迎的。[8，13-17]我们最近探索的一个有希望的途径是用合成的糖共聚物包覆SWNT，这些糖共聚物模拟细胞表面上发现的糖蛋白。[16我们证明了基于脂质封端的聚（甲基乙烯基酮）的糖基共聚物可以包覆碳纳米管（CNT）表面，并通过受体-配体相互作用促进其与细胞的结合。[16重要的是，改性的CNT对培养的细胞无毒。然而，这些发现受到CNT涂层的不规则表面和不均匀厚度的影响，这反映了所用聚合物的高多分散性（> 1.7）。[18]这种表面的异质性可能会破坏使用的glycopolymers涂层的碳纳米管作为传感器的蛋白binding. In，我们报告使用的glycodendrimers作为均匀的生物活性涂层的碳纳米管。除了各种生物医学应用外，[19-21]树枝状聚合物已被用于用光敏基团官能化CNT，[22]以改善其溶解性，[23]并引入金属检测位点。[24]它们的分支结构和高密度的外围官能团促使几个研究小组探索糖树枝状聚合物作为细胞表面聚糖的模拟物。[25-27]受这些例子以及最近使用点击化学合成树枝状聚合物的突破的启发，[28-30]我们开发了一类新的基于2，2-双（羟甲基）丙酸的双功能糖树枝状聚合物，这是一种生物相容性构建块。如方案1所示，树枝状聚合物（1）具有外围碳水化合物单元和能够通过π-π相互作用结合SWNT表面的芘尾。它们的几何形状让人联想到填充真核细胞表面的多天线N-连接聚糖。该合成采用了Sharpless和Hawker之前使用的铜（I）催化的叠氮-炔环加成（CuAAC）反应来制备不同的树枝状结构。[30在我们的工作中，CuAAC反应允许叠氮化物官能化的芘和聚糖部分分别化学选择性连接到树枝状支架的炔官能化的焦点和链端（方案1）。合成的聚糖，每个都有一个叠氮基乙基糖苷配基，[32]在糖树枝状聚合物组装过程中保持不受保护。应用该方法，我们以接近定量的产率制备了一组具有各种碳水化合物结构的[G-2]（2a-c）和[G-3]（1a-c）糖树枝状聚合物（参见参考文献[33]的命名键）。通过CuAAC将芘尾3缀合至4的焦点[25]，并且将所得树枝状聚合物5进一步与α-4-炔酸酐（6）偶联以将另外的炔基引入到外围（方案1）。然后使用CuAAC使所得树枝状聚合物7与2-叠氮基乙基单糖或二糖（8a-c）反应，得到所需的[G-3]糖树枝状聚合物1a-c。通过NMR光谱法和MALDI-TOF质谱法对树枝状聚合物进行分析，证实其结构是均匀的（参见支持信息）。通过在水溶液中超声处理将糖树枝状聚合物吸附到SWNT上（参见支持信息……
The structural, mechanical, electrical, and optical properties of single-walled carbon nanotubes (SWNTs) have stimulated considerable interest in their biological applications.[1–3] SWNTs have been employed for biosensing,[4] imaging,[5] intracellular delivery,[6] and cancer cell targeting.[7, 8] However, expanded use of SWNTs in living systems will require strategies to diminish their cytotoxicity.[9–12] Thus, surface modifications that mitigate the toxicity of SWNTs while simultaneously enabling specific biological recognition are highly sought after.[8, 13–17] A promising avenue we have recently explored is to coat SWNTs with synthetic glycopolymers that mimic the glycoproteins found on cell surfaces.[16, 17] We demonstrated that lipid-terminated poly (methyl vinyl ketone)-based glycopolymers can coat carbon nanotube (CNT) surfaces and promote their binding to cells through receptor–ligand interactions.[16, 17] Importantly, the modified CNTs were nontoxic to cultured cells. These findings were tempered, however, by the irregular surface and nonuniform thickness of the CNT coating, which reflected the high polydispersities (> 1.7) of the polymers employed.[18] Such surface heterogeneity might undermine the use of glycopolymer-coated CNTs as sensors of protein binding.Herein, we report the use of glycodendrimers as homogeneous bioactive coatings for CNTs. In addition to various biomedical applications,[19–21] dendrimers have been used to functionalize CNTs with photoactive groups,[22] to improve their solubility,[23] and to introduce sites for metal detection.[24] Their branched architectures and high density of peripheral functional groups have prompted several research groups to explore glycodendrimers as mimics of cell-surface glycans.[25–27] Inspired by these examples as well as recent breakthroughs in dendrimer synthesis using click chemistry,[28–30] we developed a new class of bifunctional glycodendrimers based on 2, 2-bis (hydroxymethyl) propionic acid, a biocompatible building block. As depicted in Scheme 1, the dendrimers (1) have peripheral carbohydrate units and a pyrene tail capable of binding SWNT surfaces through π–π interaction. Their geometry is reminiscent of the multiantenna N-linked glycans that populate eukaryotic cell surfaces. The synthesis employed the copper (I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction previously used by Sharpless and Hawker to prepare diverse dendritic structures.[30, 31] In our work, the CuAAC reaction allowed for chemoselective ligation of azide-functionalized pyrene and glycan moieties to the alkyne-functionalized focal point and chain ends of a dendritic scaffold, respectively (Scheme 1). The synthetic glycans, each with an azidoethyl aglycone,[32] remained unprotected during glycodendrimer assembly. Applying this methodology, we prepared a panel of [G-2](2a–c) and [G-3](1a–c) glycodendrimers with a variety of carbohydrate structures in near quantitative yield (see reference [33] for nomenclature key). The pyrene tail 3 was conjugated to the focal point of 4 [25] by CuAAC, and the resulting dendrimer 5 was further coupled with pent-4-ynoic anhydride (6) to introduce additional alkyne groups to the periphery (Scheme 1). The resulting dendrimer 7 was then reacted with a 2-azidoethyl mono-or disaccharide (8a–c) using CuAAC to furnish the desired [G-3] glycodendrimers 1a–c. Analysis of the dendrimers by NMR spectroscopy and MALDI-TOF mass spectrometry confirmed that the structures were homogeneous (see the Supporting Information). The glycodendrimers were adsorbed onto SWNTs by ultrasonication in aqueous solution (see the Supporting Information …