A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au-DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes,Bioconjugate Chemistry

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A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au-DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-09-07 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00504
Matthew W. Rotz ₁ , Robert J. Holbrook ₁ , Keith W. MacRenaris ₁ , Thomas J. Meade ₁

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We describe a new, and vastly superior approach for labeling spherical nucleic acid conjugates (SNAs) with diagnostic probes. SNAs have been shown to provide the unique ability to traverse the cell membrane and deliver surface conjugated DNA into cells while preserving the DNA from nuclease degradation. Our previous work on preparing diagnostically labeled SNAs was labor intensive, relatively low yielding, and costly. Here, we describe a straightforward and facile preparation for labeling SNAs with optical and MR imaging probes with significantly improved physical properties. The synthesis of Gd(III) labeled DNA Au nanoparticle conjugates is achieved by sequential conjugation of 3′-thiol-modified oligonucleotides and cofunctionalization of the particle surface with the subsequent addition of 1,2 diothiolate modified chelates of Gd(III) (abbreviated: DNA-Gd^III@AuNP). This new generation of SNA conjugates has a 2-fold increase of DNA labeling and a 1.4-fold increase in Gd(III) loading compared to published constructs. Furthermore, the relaxivity (r₁) is observed to increase 4.5-fold compared to the molecular dithiolane-Gd(III) complex, and 1.4-fold increase relative to previous particle constructs where the Gd(III) complexes were conjugated to the oligonucleotides rather than directly to the Au particle. Importantly, this simplified approach (2 steps) exploits the advantages of previous Gd(III) labeled SNA platforms; however, this new approach is scalable and eliminates modification of DNA for attaching the contrast agent, and the particles exhibit improved cell labeling.

中文翻译：

光学和MR成像探针修饰的多功能Au-DNA纳米共轭物的制备的显着改进的合成方法。

我们描述了一种新的，极为优越的方法，用诊断探针标记球形核酸共轭物（SNAs）。SNA已显示出独特的能力，可以穿越细胞膜并将表面结合的DNA传递到细胞中，同时保留DNA免受核酸酶降解的作用。我们之前在准备带有诊断标记的SNA方面的工作是劳动强度大，产量相对较低且成本高昂的。在这里，我们描述了一种简单而简便的制备方法，用于用光学和MR成像探针标记SNA，物理性质大大改善。Gd（III）标记的DNA Au纳米颗粒共轭物的合成是通过依次结合3'-硫醇修饰的寡核苷酸，颗粒表面的共官能化以及随后添加1来实现的^III @AuNP）。与已发布的构建体相比，新一代的SNA共轭物的DNA标记增加了2倍，Gd（III）负载增加了1.4倍。此外，与分子二硫杂环戊烷-Gd（III）配合物相比，观察到弛豫度（r ₁）增加了4.5倍，而相对于先前的将Gd（III）配合物与寡核苷酸结合的颗粒构建体，弛豫度（r ₁）增加了1.4倍而不是直接向金粒子。重要的是，这种简化的方法（两步）充分利用了以前带有Gd（III）标签的SNA平台的优势；但是，这种新方法具有可扩展性，并且消除了用于附着造影剂的DNA修饰，并且颗粒显示出改善的细胞标记。

更新日期：2018-09-07

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