Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell Imaging
Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell Imaging
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硫醇化合物修饰的金纳米粒子的胶体稳定性：生物共轭及其在癌细胞成像中的应用
DOI：
10.1021/la204289k
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发表时间：
2012-03-06
期刊：
影响因子：
3.9
通讯作者：
Ren, Jicun
中科院分区：
文献类型：
--
作者：
Gao, Jie;Huang, Xiangyi;Ren, Jicun
金纳米粒子（GNP）由于其特殊的物理和化学性质，是有吸引力的替代光学探针和良好的生物相容性材料。然而，GNP 有聚集的趋势，特别是在高盐和某些生物分子（例如核酸和蛋白质）存在的情况下。如何提高GNPs及其生物结合物在水溶液中的稳定性是生物应用中的关键问题。在这项研究中，我们首先在水溶液中合成了17 nm GNP，然后通过Au-S键用六种硫醇化合物对其进行修饰，包括谷胱甘肽、巯基丙酸（MPA）、半胱氨酸、胱胺、二氢硫辛酸和硫醇末端聚乙二醇（PEG-SH）。我们使用紫外-可见吸收光谱系统地研究了硫醇配体、缓冲液 pH 值和溶液盐浓度对 GNP 胶体稳定性的影响。我们发现，与其他硫醇化合物相比，用 PEG-SH 修饰的 GNP 在水溶液中最稳定。基于上述结果，我们开发了一种简单有效的方法，使用 PEG-SH 和 MPA 的混合物作为配体修饰 GNP。使用 1-乙基-3[3-(二甲基氨基)丙基]碳二亚胺和 N-羟基磺基琥珀酰亚胺作为连接试剂，这些双配体修饰的 GNP 可以轻松地与抗体缀合。我们将 GNP 与表皮生长因子受体抗体结合，并成功使用抗体-GNP 结合物作为靶向探针，利用暗场照明对癌细胞进行成像。与现有的 GNP 修饰和缀合方法相比，我们这里描述的方法简单、成本低，并且在生物测定和癌症诊断和研究中具有潜在的应用。
Gold nanoparticles (GNPs) are attractive alternative optical probes and good biocompatible materials due to their special physical and chemical properties. However, GNPs have a tendency to aggregate particularly in the presence of high salts and certain biological molecules such as nucleic acids and proteins. How to improve the stability of GNPs and their bioconjugates in aqueous solution is a critical issue in bioapplications. In this study, we first synthesized 17 nm GNPs in aqueous solution and then modified them with six thiol compounds, including glutathione, mercaptopropionic acid (MPA), cysteine, cystamine, dihydrolipoic acid, and thiol-ending polyethylene glycol (PEG-SH), via a Au-S bond. We systematically investigated the effects of the thiol ligands, buffer pH, and salt concentrations of the solutions on the colloidal stability of GNPs using UV-vis absorption spectroscopy. We found that GNPs modified with PEG-SH were the most stable in aqueous solution compared to other thiol compounds. On the basis of the above results, we developed a simple and efficient approach for modification of GNPs using a mixture of PEG-SH and MPA as ligands. These biligand-modified GNPs were facilely conjugated to antibody using 1-ethyl-3[3-(dimethylamino)propyl]carbodiimide and N-hydroxysulfosuccinimide as linkage reagents. We conjugated GNPs to epidermal growth factor receptor antibodies and successfully used the antibody-GNP conjugates as targeting probes for imaging of cancer cells using the illumination of a dark field. Compared to current methods for modification and conjugation of GNPs, our method described here is simple, has a low cost, and has potential applications in bioassays and cancer diagnostics and studies.