Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China.
Department of Radiation Oncology, Tianjin Hospital, Tianjin, 300211, PR China.
Biomaterials. 2021 Jan;268:120591. doi: 10.1016/j.biomaterials.2020.120591. Epub 2020 Dec 8.
DNA nanoflower has been demonstrated as a promising DNA nanostructure for therapeutics and bioimaging primarily because of the programmable DNA sequence and unique structure. Herein, we report manganese ions mediated enzymatic biomineralization to prepare DNA-Mn hybrid nanoflower (DMNF). Paramagnetic Mn was explored as the co-factor of DNA polymerase for the extension of long strand DNA. The biomimetic synthesis of DMNF was performed using the long strand DNA as template via nucleation and growth of MnPPi. The morphology and size of DMNF were controllable by tuning reaction time and Mn concentration. The aptamer sequence was encoded into circle template to achieve tumor-targeted DMNF, and cellular uptake assay demonstrated obvious aptamer-mediated internalization. DMNF showed enhanced T-weighted magnetic resonance (MR) imaging effect in acid environment for high tumor-specific MR imaging, and high spatial resolution imaging of kidneys and liver. Our work provides a facile enzymatically biomineral strategy to integrate multifunctional modules into one DNA structure and promotes the development of DNA nanostructure for precision medicine.
DNA 纳米花因其可编程的 DNA 序列和独特的结构,已被证明是一种很有前途的用于治疗和生物成像的 DNA 纳米结构。在此,我们报告了锰离子介导的酶促生物矿化,以制备 DNA-Mn 杂化纳米花 (DMNF)。我们探索了顺磁性 Mn 作为 DNA 聚合酶的辅助因子,用于长链 DNA 的延伸。通过 MnPPi 的成核和生长,以长链 DNA 为模板,仿生合成了 DMNF。通过调节反应时间和 Mn 浓度,可以控制 DMNF 的形态和尺寸。将适体序列编码到圆形模板中,实现了肿瘤靶向的 DMNF,细胞摄取实验证明了明显的适体介导的内化。DMNF 在酸性环境下表现出增强的 T 加权磁共振 (MR) 成像效应,用于高肿瘤特异性的 MR 成像,以及肾脏和肝脏的高空间分辨率成像。我们的工作提供了一种简便的酶促生物矿化策略,将多功能模块集成到一个 DNA 结构中,促进了 DNA 纳米结构在精准医疗中的发展。