Carboxylation of multiwalled carbon nanotubes (MWCNTs) has been used to improve solubility in aqueous systems and for further functionalization with biologically active moieties for biomedical uses. An important consideration is that oxidation debris is generated during the process of carboxylation, which can be removed by base washing. We hypothesized that surface modification as well as purification by debris removal may alter physicochemical properties of MWCNTs and their ability to bind proteins. We utilized pristine MWCNT, carboxylated MWCNTs (F-MWCNTs), and base-washed carboxylated MWCNTs (BW-F-MWCNTs) to examine formation of a bovine serum albumin (BSA) protein corona and impact on biological responses. We found that carboxylation increased the capability of F-MWCNTs to bind BSA, and base washing further increased this binding. Functionalization increased cellular uptake by rat aortic endothelial cells (RAEC) and mouse macrophages (RAW264.7), while base washing showed results similar to the functionalized analog. Interestingly, BSA binding downregulated mRNA levels of interleukin-6 (IL-6) and heme oxygenase 1 (Hmox1) in RAEC cells but upregulated the expression of IL-6 and Hmox1 in RAW264.7 cells. Overall, our study demonstrated that surface modification as well as further purification impacted the interaction of MWCNTs with proteins and subsequent cellular responses.

中文翻译：

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多壁碳纳米管表面修饰和纯化对牛血清白蛋白结合和生物学响应的影响。

多壁碳纳米管（MWCNT）的羧基化已被用于改善在水性体系中的溶解度，并用于生物医学用途的具有生物活性部分的进一步功能化。一个重要的考虑因素是，在羧化过程中会产生氧化碎片，可以通过碱洗将其清除。我们假设表面改性以及通过碎片清除进行纯化可能会改变MWCNT的理化特性及其结合蛋白的能力。我们利用原始的MWCNT，羧基化的MWCNTs（F-MWCNTs）和碱洗的羧基化的MWCNTs（BW-F-MWCNTs）来检查牛血清白蛋白（BSA）蛋白电晕的形成及其对生物学反应的影响。我们发现羧化增加了F-MWCNTs结合BSA的能力，碱洗进一步增强了这种结合。功能化增加了大鼠主动脉内皮细胞（RAEC）和小鼠巨噬细胞（RAW264.7）的细胞摄取，而碱洗显示的结果与功能化类似物相似。有趣的是，BSA结合可下调RAEC细胞中白介素6（IL-6）和血红素加氧酶1（Hmox1）的mRNA水平，但上调RAW264.7细胞中IL-6和Hmox1的表达。总体而言，我们的研究表明，表面修饰以及进一步纯化会影响MWCNT与蛋白质的相互作用以及随后的细胞反应。BSA结合可下调RAEC细胞中白介素6（IL-6）和血红素加氧酶1（Hmox1）的mRNA水平，但上调RAW264.7细胞中IL-6和Hmox1的表达。总体而言，我们的研究表明，表面修饰以及进一步纯化会影响MWCNT与蛋白质的相互作用以及随后的细胞反应。BSA结合可下调RAEC细胞中白介素6（IL-6）和血红素加氧酶1（Hmox1）的mRNA水平，但上调RAW264.7细胞中IL-6和Hmox1的表达。总体而言，我们的研究表明，表面修饰以及进一步纯化会影响MWCNT与蛋白质的相互作用以及随后的细胞反应。