Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

纳米技术具有许多优点，在这里我们报告了将RNA纳米技术用于方向控制的优势。更改了箭头形RNA的方向，以控制配体在胞外囊泡膜上的显示，以实现特定的细胞靶向，或调节小干扰RNA（siRNA）或microRNA（miRNA）的细胞内运输。在箭头的尾部放置锚定膜的胆固醇会导致RNA适体或叶酸显示在细胞外囊泡的外表面。相反，将胆固醇置于箭头处会导致RNA纳米颗粒部分装载到细胞外囊泡中。利用RNA配体的特异性靶向作用和细胞外囊泡的有效膜融合作用，所得的展示配体的细胞外囊泡能够将siRNA特异性递送至细胞，并在三种癌症模型中有效地阻断了肿瘤的生长。胞外小泡表现出与前列腺特异性膜抗原结合的适体，并带有survivin siRNA，可抑制前列腺癌的异种移植。相同的细胞外小泡反而表现出表皮生长因子受体适体抑制原位乳腺癌模型。同样，survivin siRNA加载和叶酸展示细胞外囊泡抑制患者源性结直肠癌异种移植。相同的细胞外小泡反而表现出表皮生长因子受体适体抑制原位乳腺癌模型。同样，survivin siRNA加载和叶酸展示细胞外囊泡抑制患者源性结直肠癌异种移植。相同的细胞外小泡反而表现出表皮生长因子受体适体抑制原位乳腺癌模型。同样，survivin siRNA加载和叶酸展示细胞外囊泡抑制患者源性结直肠癌异种移植。