DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties
DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties
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用于癌症治疗的 DNA 折纸递送系统，具有可调释放特性。
DOI：
10.1021/nn3022662
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发表时间：
2012-10-01
期刊：
影响因子：
17.1
通讯作者：
Hogberg, Bjorn
中科院分区：
文献类型：
--
作者：
Zhao, Yong-Xing;Shaw, Alan;Hogberg, Bjorn
在DNA纳米结构的组装中，沃森-克里克碱基配对的特异性被用来控制纳米尺度的物质。使用这种技术进行药物递送是实现魔术子弹概念的一种有前途的途径，因为它将允许实现在一个纳米结构中共定位药物、靶向配体和其他功能的复杂组装。蒽环类药物在癌症治疗中的作用机制是嵌入DNA，由于DNA纳米技术允许如此高程度的定制，我们假设这将使我们能够调整DNA纳米结构，以便将蒽环类药物多柔比星（Dox）最佳地递送到人类乳腺癌细胞。我们已经在三种不同的乳腺癌细胞系（MDA-MB-231、MDA-MB-468和MCF-7）上测试了两种DNA折纸纳米结构。不同的纳米结构被设计成表现出不同程度的整体扭曲，导致DNA双螺旋结构中不同程度的松弛。通过调整纳米结构设计，我们能够（i）调整药物的包封效率和释放速率，以及（ii）当与游离Dox相比时，增加细胞毒性并降低细胞内消除速率。使用流式细胞术研究了递送系统在乳腺癌细胞中诱导的增强的凋亡。研究结果表明，DNA折纸纳米结构代表了Dox的有效递送系统，导致高度内化和乳腺癌细胞中程序性细胞死亡的诱导增加。此外，通过设计的结构表现出不同程度的扭曲，我们能够合理地控制和定制的药物释放动力学。
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.