Spherical and porous nanoparticles are ideal nanostructures for drug delivery. But currently they are mainly composed of non-degradable inorganic materials, which hinder clinical applications. Here, biological porous nanospheres using RNA as the building blocks and cyclodextrin as the adhesive were synthesized. The RNA contained the aptamer of EpCAM for targeting delivery and siRNA for gene silencing of EpCAM, while cyclodextrin could load insoluble sorafenib, the core drug of targeted therapy for hepatocellular carcinoma (HCC), through its hydrophobic cavity. After being internalized into targeted HCC cells under the assistance of the aptamer, the porous nanospheres could be degraded by the cytoplasmic Dicer enzymes, releasing siRNA and sorafenib for synergistic therapy. The synergistic efficacy of the porous RNA nanospheres has been validated at in vitro function assay, subcutaneous tumor bearing mice, and orthotopic tumor bearing mice in vivo models. In view of the broad prospects of synergy of gene therapy with chemotherapy, and the fact that RNA and cyclodextrin of the porous nanospheres can be extended to load various types of siRNA and small molecule drugs, respectively, this form of biological porous nanospheres offers opportunities for targeted delivery of suitable drugs for treatment of specific tumors.

球形和多孔纳米颗粒是用于药物递送的理想纳米结构。但是目前它们主要由不可降解的无机材料组成，这阻碍了临床应用。在这里，合成了以RNA为构建基和环糊精为粘合剂的生物多孔纳米球。RNA包含用于靶向递送的EpCAM适体和用于沉默EpCAM基因沉默的siRNA，而环糊精则可以通过疏水腔加载不溶性索拉非尼，索拉非尼是肝细胞癌靶向治疗的核心药物。在适体的帮助下被内化成靶向HCC细胞后，多孔纳米球可被细胞质Dicer酶降解，释放siRNA和索拉非尼以进行协同治疗。多孔RNA纳米球的协同功效已在体外功能测定，皮下荷瘤小鼠和原位荷瘤小鼠体内模型。鉴于基因疗法与化学疗法协同作用的广阔前景，以及多孔纳米球的RNA和环糊精可以扩展以分别装载各种类型的siRNA和小分子药物的事实，这种形式的生物多孔纳米球为生物纳米球的发展提供了机会。有针对性地递送用于治疗特定肿瘤的合适药物。