Zhong Cheng, Shi Zhanquan, Liu Chia-Yang, Binzel Daniel W, Jin Kai, Li Xin, Guo Peixuan, Li S Kevin
Division of Pharmaceutical Sciences, James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA.
Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Pharmaceutics. 2025 Jan 3;17(1):55. doi: 10.3390/pharmaceutics17010055.
RNA nanoparticles, derived from the packaging RNA three-way junction motif (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor, have been demonstrated to be thermodynamically and chemically stable, with promise as a nanodelivery system. : A previous study showed that RNA nanoparticles with antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) inhibited cell proliferation via WST-1 assay. To further investigate the antiangiogenic potential of these RNA nanoparticles, a modified three-dimensional (3D) spheroid sprouting assay model of human umbilical vein endothelial cells was utilized in the present study. : Three groups of RNA nanoparticles were evaluated, namely, pRNA-3WJ series, RNA square series (polygon-type RNA nanoparticles), and 8WJ series (multiple-way junction RNA nanoparticles), which were conjugated with a single anti-VEGF, the combination of one anti-VEGF and one anti-Ang2, or multiple anti-VEGF aptamers. The core scaffold RNA nanoparticles (without aptamers) were used as the references, and bevacizumab was used as the positive control. : The results demonstrated the inhibition effects of the RNA nanoparticles on endothelial cell tube formation at 67 nM in a 3D spheroid sprouting model. The results in the 3D spheroid sprouting assay are consistent with those of the WST-1 proliferation assays. : Among the RNA nanoparticles evaluated, 3WJ-3VEGF and SQR-VEGF-Ang2 had inhibition effects equivalent to bevacizumab and were promising for anti-angiogenesis treatment.
源自噬菌体phi29 DNA包装马达的包装RNA三向连接基序（pRNA-3WJ）的RNA纳米颗粒已被证明在热力学和化学上是稳定的，有望成为一种纳米递送系统。：先前的一项研究表明，带有抗血管生成适体（抗血管内皮生长因子（VEGF）和抗血管生成素-2（Ang2）适体）的RNA纳米颗粒通过WST-1测定法抑制细胞增殖。为了进一步研究这些RNA纳米颗粒的抗血管生成潜力，本研究采用了改良的人脐静脉内皮细胞三维（3D）球体发芽测定模型。：评估了三组RNA纳米颗粒，即pRNA-3WJ系列、RNA方形系列（多边形型RNA纳米颗粒）和8WJ系列（多向连接RNA纳米颗粒），它们分别与单个抗VEGF、一种抗VEGF和一种抗Ang2的组合或多个抗VEGF适体偶联。核心支架RNA纳米颗粒（无适体）用作对照，贝伐单抗用作阳性对照。：结果表明，在3D球体发芽模型中，67 nM的RNA纳米颗粒对内皮细胞管形成有抑制作用。3D球体发芽测定的结果与WST-1增殖测定的结果一致。：在所评估的RNA纳米颗粒中，3WJ-3VEGF和SQR-VEGF-Ang2具有与贝伐单抗相当的抑制作用，有望用于抗血管生成治疗。
