Xu Congcong, Zhang Kaiming, Yin Hongran, Li Zhefeng, Krasnoslobodtsev Alexey, Zheng Zhen, Ji Zhouxiang, Guo Sijin, Li Shanshan, Chiu Wah, Guo Peixuan
Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Department of Bioengineering, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
Nano Res. 2020 Dec;13(12):3241-3247. doi: 10.1007/s12274-020-2996-1. Epub 2020 Sep 4.
Ribonucleic acid (RNA) nanotechnology platforms have the potential of harboring therapeutics for delivery in disease treatment. However, the nonspecific interaction between the harbored hydrophobic drugs and cells or other components before reaching the diseased site has been an obstacle in drug delivery. Here we report an encapsulation strategy to prevent such nonspecific hydrophobic interactions and based on a self-assembled three-dimensional (3D) RNA nanocage. By placing an RNA three-way junction (3WJ) in the cavity of the nanocage, the conjugated hydrophobic molecules were specifically positioned within the nanocage, preventing their exposure to the biological environment. The assembly of the nanocages was characterized by native polyacrylamide gel electrophoresis (PAGE), atomic force microscopy (AFM), and cryogenic electron microscopy (cryo-EM) imaging. The stealth effect of the nanocage for hydrophobic molecules was evaluated by gel electrophoresis, flow cytometry, and confocal microscopy. The sheathing effect of the nanocage for hydrophobic molecules was assessed by biodistribution profiling in mice. The RNA nanocages with hydrophobic biomolecules underwent faster clearance in liver and spleen in comparison to their counterparts. Therefore, this encapsulation strategy holds promise for delivery of hydrophobic drugs for disease treatment.
核糖核酸（RNA）纳米技术平台有潜力承载用于疾病治疗的递送药物。然而，在到达病变部位之前，所承载的疏水性药物与细胞或其他成分之间的非特异性相互作用一直是药物递送中的一个障碍。在此，我们报道一种基于自组装三维（3D）RNA纳米笼的封装策略，以防止此类非特异性疏水相互作用。通过在纳米笼的腔内放置一个RNA三向连接点（3WJ），共轭疏水分子被特异性地定位在纳米笼内，从而防止它们暴露于生物环境中。纳米笼的组装通过非变性聚丙烯酰胺凝胶电泳（PAGE）、原子力显微镜（AFM）和低温电子显微镜（cryo-EM）成像进行表征。纳米笼对疏水分子的隐身效应通过凝胶电泳、流式细胞术和共聚焦显微镜进行评估。纳米笼对疏水分子的包裹效应通过在小鼠体内的生物分布分析进行评估。与不含疏水生物分子的纳米笼相比，含有疏水生物分子的RNA纳米笼在肝脏和脾脏中的清除速度更快。因此，这种封装策略有望用于递送疏水性药物进行疾病治疗。
