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

A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au-DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes.
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一种明显改进的合成方法,用于制备多功能Au-DNA纳米粒子结合物,并用光学和MR成像探针修饰。

DOI:
10.1021/acs.bioconjchem.8b00504
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发表时间:
2018-11-21
影响因子:
4.7
通讯作者:
Meade TJ
Meade TJ
中科院分区:
化学2区
文献类型:
--
作者:
Rotz MW;Holbrook RJ;MacRenaris KW;Meade TJ

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我们描述了一种新的,非常上级的方法标记球形核酸共轭物(SNA)与诊断探针。SNA已经显示出提供穿过细胞膜并将表面缀合的DNA递送到细胞中同时保护DNA免于核酸酶降解的独特能力。我们以前的工作,准备诊断标记的SNA是劳动密集型的,相对较低的产量,和昂贵的。在这里,我们描述了一个简单和方便的准备标记SNA与光学和MR成像探针具有显着改善的物理性能。Gd(III)标记的DNA Au纳米颗粒缀合物的合成是通过3 ′-巯基修饰的寡核苷酸的顺序缀合和颗粒表面的共官能化以及随后添加Gd(III)的1,2二硫醇盐修饰的螯合物(缩写:DNA-GdIII@AuNP)来实现的。与已发表的构建体相比,这种新一代SNA缀合物具有2倍的DNA标记增加和1.4倍的Gd(III)负载增加。此外,观察到弛豫率(r1)与分子二硫戊环-Gd(III)络合物相比增加4.5倍,并且相对于其中Gd(III)络合物与寡核苷酸缀合而不是直接与Au颗粒缀合的先前颗粒构建体增加1.4倍。重要的是,这种简化的方法(2个步骤)利用了先前Gd(III)标记SNA平台的优点;然而,这种新方法是可扩展的,消除了用于附着造影剂的DNA修饰,并且颗粒表现出改善的细胞标记。
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-GdIII@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.
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