Toehold-Mediated Shape Transition of Nucleic Acid Nanoparticles
Toehold-Mediated Shape Transition of Nucleic Acid Nanoparticles
复制标题
DOI：
10.1021/acsami.3c01604
复制
发表时间：
2023-05-19
影响因子：
9.5
通讯作者：
Khisamutdinov，Emil F.
中科院分区：
文献类型：
--
作者：
Hartung，Jordan;McCann，Nathan;Khisamutdinov，Emil F.
我们介绍了一个立足点介导的链置换策略，用于核酸纳米颗粒（NANP）的形状转换，使其在等温条件下从三角形到六边形结构的顺序转变。通过电泳迁移率变动分析、原子力显微镜和动态光散射证实了成功的形状转变。此外，分离荧光适体的实施允许真实的时间监测个体转变。三种不同的RNA适体-孔雀石绿色（MG），花椰菜，芒果-被嵌入NANP作为报告结构域，以确认形状转换。虽然MG在正方形、五边形和六边形结构中“点亮”，但西兰花仅在形成五边形和六边形NANP时被激活，而芒果仅报告六边形的存在。此外，所设计的RNA荧光平台可以用于构建逻辑门，该逻辑门通过实施非顺序多边形变换方法与三个单链RNA输入进行AND运算。重要的是，多边形支架显示出作为药物递送剂和生物传感器的有前途的潜力。所有的多边形表现出有效的细胞内化，随后特异性基因沉默时，装饰有荧光团和RNAi诱导剂。这项工作提供了一个新的角度为立足点介导的形状转换纳米器件的设计，以激活不同的发光适体的生物传感器，逻辑门，和治疗设备的发展，在核酸纳米技术。
We introduce a toehold-mediated strand displacement strategy for regulated shape-switching of nucleic acid nanoparticles (NANPs) enabling their sequential transformation from triangular to hexagonal architectures at isothermal conditions. The successful shape transitions were confirmed by electrophoretic mobility shift assays, atomic force microscopy, and dynamic light scattering. Furthermore, implementation of split fluorogenic aptamers allowed for monitoring the individual transitions in real time. Three distinct RNA aptamers─malachite green (MG), broccoli, and mango─were embedded within NANPs as reporter domains to confirm shape transitions. While MG “lights up” within the square, pentagonal, and hexagonal constructs, the broccoli is activated only upon formation of pentagon and hexagon NANPs, and mango reports only the presence of hexagons. Moreover, the designed RNA fluorogenic platform can be employed to construct a logic gate that performs an AND operation with three single-stranded RNA inputs by implementing a non-sequential polygon transformation approach. Importantly, the polygonal scaffolds displayed promising potential as drug delivery agents and biosensors. All polygons exhibited effective cellular internalization followed by specific gene silencing when decorated with fluorophores and RNAi inducers. This work offers a new perspective for the design of toehold-mediated shape-switching nanodevices to activate different light-up aptamers for the development of biosensors, logic gates, and therapeutic devices in the nucleic acid nanotechnology.