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ACS Nano:利用低扭曲度DNA折纸术运送药物到肿瘤

来源:生物谷 2012-09-17 10:32

2012年9月16日 讯 /生物谷BIOON/ --在一项新的研究中,来自瑞典卡罗林斯卡学院的研究人员描述了所谓的DNA折纸术(DNA origami )能够加强某些细胞抑制剂在治疗癌症中的疗效。在现代纳米技术的帮助下,研究人员能够将药物直接靶向肿瘤,同时让周围的健康组织不受伤害。

抗肿瘤药物阿霉素(doxorubicin)长期被用作一种细胞抑制剂来治疗癌症,但是也能够导致严重性毒副作用,如心肌梗塞和严重性恶心。正因为此,科学家们一直试图找到一种方法来运送这种药物到病变部位的肿瘤细胞之中。

在当前刊登在ACS Nano期刊上的这项研究中,来自卡罗林斯卡学院的研究人员展示DNA折纸术如何能够被用作阿霉素的载体。DNA折纸术是一种构建DNA纳米结构的新技术。利用这种技术,研究人员能够产生高度复杂的纳米结构,同时蛋白和其他分子也能够轻松地被附着到这种结构的表面上。

在这种情形下,研究人员利用DNA折纸术构建的DNA纳米结构将阿霉素包裹在内,同时降低DNA双螺旋的扭曲程度。这允许这种药物更加缓慢地释放,并且在比之前更低的浓度下更加有效地作用于癌细胞。

论文通信作者Björn Högberg博士说,“当DNA拥有较低的扭曲度时,就有更多的空间允许阿霉素附着上去,这就导致这种药物更加缓慢地释放。利用DNA折纸术的另一个优势在于我们能够快速地开发出靶标蛋白系统。这将让我们能够以一种更加不会伤害健康细胞的方式运送药物。”(生物谷Bioon.com)

DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties

Yong-Xing Zhao †‡, Alan Shaw †, Xianghui Zeng †, Erik Benson †, Andreas M. Nyström †, and Björn Högberg

In the assembly of DNA nanostructures, the specificity of Watson–Crick base pairing is used to control matter at the nanoscale. Using this technology for drug delivery is a promising route toward the magic bullet concept, as it would allow the realization of complex assemblies that co-localize drugs, targeting ligands and other functionalities in one nanostructure. Anthracyclines' mechanism of action in cancer therapy is to intercalate DNA, and since DNA nanotechnology allows for such a high degree of customization, we hypothesized that this would allow us to tune the DNA nanostructures for optimal delivery of the anthracycline doxorubicin (Dox) to human breast cancer cells. We have tested two DNA origami nanostructures on three different breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7). The different nanostructures were designed to exhibit varying degrees of global twist, leading to different amounts of relaxation in the DNA double-helix structure. By tuning the nanostructure design we are able to (i) tune the encapsulation efficiency and the release rate of the drug and (ii) increase the cytotoxicity and lower the intracellular elimination rate when compared to free Dox. Enhanced apoptosis induced by the delivery system in breast cancer cells was investigated using flow cytometry. The findings indicate that DNA origami nanostructures represent an efficient delivery system for Dox, resulting in high degrees of internalization and increased induction of programmed cell death in breast cancer cells. In addition, by designing the structures to exhibit different degrees of twist, we are able to rationally control and tailor the drug release kinetics.

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