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2'-氟阿拉伯核酸纳米结构作为在强酸性环境中用于细胞递送的稳定载体

2'-Fluoroarabinonucleic Acid Nanostructures as Stable Carriers for Cellular Delivery in the Strongly Acidic Environment.

作者信息

Wang Qian, Chen Xiaoxing, Li Xintong, Song Dongfan, Yang Jintao, Yu Hanyang, Li Zhe

机构信息

Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu 210023, China.

State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210023, China.

出版信息

ACS Appl Mater Interfaces. 2020 Dec 2;12(48):53592-53597. doi: 10.1021/acsami.0c11684. Epub 2020 Nov 18.

DOI:10.1021/acsami.0c11684
PMID:33206496
Abstract

DNA nanotechnology is powerful in constructing programmable nanostructures with distinct dimensions, sizes, and shapes. However, natural DNA molecules are prone to nuclease degradation, thus limiting the applications of such DNA nanostructures. 2'-Fluoroarabinonucleic acid (FANA) is a chemically modified oligonucleotide with similar base pairing properties to DNA and exhibits superior physical and chemical stabilities. In this work, FANA molecules were used to construct double crossover nanostructures, and it was demonstrated that incorporation of FANA conferred nucleic acid nanostructures with increased thermal stability and stronger nuclease resistance. More importantly, FANA nanostructures were able to maintain the structural integrity in the strongly acidic environment (pH 1.2). Last, such FANA nanostructures functioned well in acting as stable carriers of small-molecule cargoes for cellular delivery in simulated gastric fluid, while the DNA counterparts were mostly degraded. Collectively, these results demonstrated that FANA self-assembly was not only a substantial complement to the structural DNA nanotechnology but also an appealing molecular tool for biomedical applications.

摘要

DNA纳米技术在构建具有不同维度、尺寸和形状的可编程纳米结构方面具有强大功能。然而,天然DNA分子易于被核酸酶降解,从而限制了此类DNA纳米结构的应用。2'-氟阿拉伯核酸(FANA)是一种化学修饰的寡核苷酸,其碱基配对特性与DNA相似,并且具有卓越的物理和化学稳定性。在这项工作中,FANA分子被用于构建双交叉纳米结构,结果表明,掺入FANA可赋予核酸纳米结构更高的热稳定性和更强的核酸酶抗性。更重要的是,FANA纳米结构能够在强酸性环境(pH 1.2)中保持结构完整性。最后,此类FANA纳米结构在模拟胃液中作为小分子货物的稳定载体用于细胞递送时表现良好,而DNA对应物大多被降解。总体而言,这些结果表明,FANA自组装不仅是对结构性DNA纳米技术的重要补充,也是一种用于生物医学应用的有吸引力的分子工具。

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