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Targeted Delivery of Rab26 siRNA with Precisely Tailored DNA Prism for Lung Cancer Therapy.
ChemBioChem ( IF 2.6 ) Pub Date : 2019-02-27 , DOI: 10.1002/cbic.201800761
Qian Liu 1 , Dong Wang 1 , Zhi Xu 1 , Chunji Huang 2 , Chun Zhang 1 , Binfeng He 1 , Chengde Mao 3 , Guansong Wang 1 , Hang Qian 1
Affiliation  

Programmable DNA nanostructures are a new class of biocompatible, nontoxic nanomaterials. Nevertheless, their application in the field of biomedical research is still in its infancy, especially as drug delivery vehicles for gene therapy. In this study, a GTPase Rab26 was investigated as a new potential therapeutic target using a precisely tailored DNA nanoprism for targeted lung cancer therapy. Specifically, a DNA nanoprism platform with tunable targeting and siRNA loading capability is designed and synthesized. The as-prepared DNA prisms were decorated with two functional units: a Rab26 siRNA as the drug and MUC-1 aptamers as a targeting moiety for non-small cell lung cancer. The number and position of both siRNA and MUC-1 aptamers can be readily tuned by switching two short, single-stranded DNA. Native polyacrylamide gel electrophoresis (PAGE) and dynamic light scattering technique (DLS) demonstrate that all nanoprisms with different functionalities are self-assembled with high yield. It is also found that the cellular uptake of DNA prisms is proportional to the aptamer number on each nanoprism, and the as-prepared DNA nanoprism show excellent anti-cancer activities and targeting capability. This study suggests that by careful design, self-assembled DNA nanostructures are highly promising, customizable, multifunctional nanoplatforms for potential biomedical applications, such as personalized precision therapy.

中文翻译:

Rab26 siRNA的靶向递送与精确定制的DNA棱镜一起用于肺癌治疗。

可编程DNA纳米结构是一类新的生物相容性,无毒的纳米材料。然而,它们在生物医学研究领域的应用仍处于起步阶段,特别是作为基因治疗的药物传递载体。在这项研究中,对GTPase Rab26作为新的潜在治疗靶标进行了研究,使用精确定制的DNA纳米棱镜进行靶向肺癌治疗。具体而言,设计并合成了具有可调靶点和siRNA装载功能的DNA纳米棱镜平台。所制备的DNA棱镜装饰有两个功能单元:Rab26 siRNA作为药物和MUC-1适体作为非小细胞肺癌的靶向部分。siRNA和MUC-1适体的数量和位置都可以通过切换两个短的单链DNA轻松进行调节。天然聚丙烯酰胺凝胶电泳(PAGE)和动态光散射技术(DLS)证明,具有不同功能的所有纳米棱镜都可以高效率地自组装。还发现DNA棱镜的细胞摄取与每个纳米棱镜上的适体数成比例,并且所制备的DNA纳米棱镜显示出优异的抗癌活性和靶向能力。这项研究表明,通过仔细的设计,自组装的DNA纳米结构对于潜在的生物医学应用(例如个性化的精确治疗)是非常有前途的,可定制的多功能纳米平台。还发现DNA棱镜的细胞摄取与每个纳米棱镜上的适体数成比例,并且所制备的DNA纳米棱镜显示出优异的抗癌活性和靶向能力。这项研究表明,通过仔细的设计,自组装的DNA纳米结构对于潜在的生物医学应用(例如个性化的精确治疗)是非常有前途的,可定制的多功能纳米平台。还发现DNA棱镜的细胞摄取与每个纳米棱镜上的适体数成比例,并且所制备的DNA纳米棱镜显示出优异的抗癌活性和靶向能力。这项研究表明,通过仔细的设计,自组装的DNA纳米结构对于潜在的生物医学应用(例如个性化的精确治疗)是非常有前途的,可定制的多功能纳米平台。
更新日期:2019-02-27
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