Han Liting, Song Tao, Wang Xinyu, Luo Yan, Gu Chuanqi, Li Xin, Wen Jinda, Wen Zhibin, Shi Xiaolong
Department of Gynecology 2, Renmin Hospital of Wuhan University, Wuhan, China.
College of Computer Science and Technology, China University of Petroleum (East China), Qingdao, China.
Comput Struct Biotechnol J. 2024 Mar 1;24:196-204. doi: 10.1016/j.csbj.2024.02.021. eCollection 2024 Dec.
In recent years, DNA origami-based nanocarriers have been extensively utilized for efficient cancer therapy. However, developing a nanocarrier capable of effectively protecting cargos such as RNA remains a challenge. In this study, we designed a compact and controllable DNA tubular origami (DTO) measuring 120 nm in length and 18 nm in width. The DTO exhibited appropriate structural characteristics for encapsulating and safeguarding cargo. Inside the DTO, we incorporated 20 connecting points to facilitate the delivery of cargoes to various ovarian and normal epithelial cell lines. Specifically, fluorescent-labeled DNA strands were attached to these sites as cargoes. The DTO was engineered to open upon encountering miR-21 through RNA/DNA strand displacement. Significantly, for the first time, we inhibited fluorescence using the compact DNA nanotube and observed dynamic fluorescent signals, indicating the controllable opening of DTO through live-cell imaging. Our results demonstrated that the DTO remained properly closed, exhibited effective internalization in ovarian cancer cells in vitro, showcasing marked differential expression of miR-21, and efficiently opened with short-term exposure to miR-21. Leveraging its autonomous behavior and compact design, the DTO emerges as a promising nanocarrier for various clinically relevant materials. It holds significant application prospects in anti-cancer therapy and the development of flexible biosensors.
近年来,基于DNA折纸的纳米载体已被广泛用于高效的癌症治疗。然而,开发一种能够有效保护RNA等货物的纳米载体仍然是一项挑战。在本研究中,我们设计了一种紧凑且可控的DNA管状折纸(DTO),其长度为120纳米,宽度为18纳米。DTO展现出适合封装和保护货物的结构特征。在DTO内部,我们纳入了20个连接点,以促进货物向各种卵巢和正常上皮细胞系的递送。具体而言,荧光标记的DNA链作为货物附着于这些位点。DTO经设计可在遇到miR-21时通过RNA/DNA链置换而打开。重要的是,我们首次使用紧凑的DNA纳米管抑制荧光并观察到动态荧光信号,这表明通过活细胞成像可实现DTO的可控打开。我们的结果表明,DTO保持适当关闭状态,在体外卵巢癌细胞中表现出有效的内化,显示出miR-21的明显差异表达,并在短期暴露于miR-21时有效打开。凭借其自主行为和紧凑设计,DTO成为用于各种临床相关材料的有前途的纳米载体。它在抗癌治疗和柔性生物传感器的开发中具有重要的应用前景。