Conjugation of antibodies to gold nanorods through Fc portion: synthesis and molecular specific imaging.
Conjugation of antibodies to gold nanorods through Fc portion: synthesis and molecular specific imaging.
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DOI：
10.1021/bc3004815
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发表时间：
2013-06-19
影响因子：
4.7
通讯作者：
Sokolov, Konstantin V.
中科院分区：
文献类型：
--
作者：
Joshi, Pratixa P.;Yoon, Soon Joon;Hardin, William G.;Emelianov, Stanislav;Sokolov, Konstantin V.
各向异性的金纳米棒提供了一种方便的特性组合，例如等离子体共振的可调谐性和近红外到红色光谱区域中的强消光截面。这些性质已经在开发用于合成靶向纳米棒的抗体缀合方法中产生了显著的兴趣，所述靶向纳米棒用于许多生物医学应用，包括分子特异性成像和治疗。先前公开的缀合方法已经实现了分子特异性。然而，目前的缀合方法具有几个缺点，包括通过静电相互作用产生的生物缀合物的低稳定性和潜在的细胞毒性，以及在共价缀合期间缺乏对抗体取向的控制。在这里，我们通过在金纳米棒表面引入定向抗体缀合来解决这些缺点。定向缀合通过碳水化合物部分实现，碳水化合物部分位于大多数抗体的Fc部分的重链之一上。碳水化合物在温和条件下被氧化成酰肼反应性醛基。然后，使用具有酰肼和二硫醇基团的异功能连接体将抗体连接到金纳米棒。使用电子显微镜、zeta电位和消光光谱表征定向共轭方法。我们还确定了与纳米棒聚集相关的光谱变化;这些光谱变化可以用作纳米棒生物缀合物的方便的质量控制。使用癌细胞培养模型的高光谱光学和光声成像证明了合成的抗体靶向纳米棒的分子特异性。此外，我们观察到分子特异性纳米棒与癌细胞相互作用后光谱的特征变化;观察到的光谱特征可以用于敏感的癌症检测。
Anisotropic gold nanorods provide a convenient combination of properties, such as tunability of plasmon resonances and strong extinction cross-sections in the near-infrared to red spectral region. These properties have created significant interest in the development of antibody conjugation methods for synthesis of targeted nanorods for a number of biomedical applications, including molecular specific imaging and therapy. Previously published conjugation approaches have achieved molecular specificity. However, the current conjugation methods have several downsides including low stability and potential cytotoxicity of bioconjugates that are produced by electrostatic interactions as well as lack of control over antibody orientation during covalent conjugation. Here we addressed these shortcomings by introducing directional antibody conjugation to the gold nanorod surface. The directional conjugation is achieved through the carbohydrate moiety, which is located on one of the heavy chains of the Fc portion of most antibodies. The carbohydrate is oxidized under mild conditions to a hydrazide reactive aldehyde group. Then, a heterofunctional linker with hydrazide and dithiol groups is used to attach antibodies to gold nanorods. The directional conjugation approach was characterized using electron microscopy, zeta potential and extinction spectra. We also determined spectral changes associated with nanorod aggregation; these spectral changes can be used as a convenient quality control of nanorod bioconjugates. Molecular specificity of the synthesized antibody targeted nanorods was demonstrated using hyperspectral optical and photoacoustic imaging of cancer cell culture models. Additionally, we observed characteristic changes in optical spectra of molecular specific nanorods after their interactions with cancer cells; the observed spectral signatures can be explored for sensitive cancer detection.
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影响因子：
10.8
作者：
Eghtedari M;Liopo AV;Copland JA;Oraevsky AA;Motamedi M
通讯作者：
Motamedi M
影响因子：
10.8
作者：
Durr, Nicholas J.;Larson, Timothy;Ben-Yakar, Adela
通讯作者：
Ben-Yakar, Adela
DOI：
10.1073/pnas.2232479100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hirsch, LR;Stafford, RJ;West, JL
通讯作者：
West, JL
影响因子：
17.1
作者：
Bharill S;Chen C;Stevens B;Kaur J;Smilansky Z;Mandecki W;Gryczynski I;Gryczynski Z;Cooperman BS;Goldman YE
通讯作者：
Goldman YE
影响因子：
10.8
作者：
Chen, Jingyi;Wang, Danling;Li, Xingde
通讯作者：
Li, Xingde