Cyclodextrin-mediated formation of porous RNA nanospheres and their application in synergistic targeted therapeutics of hepatocellular carcinoma
Cyclodextrin-mediated formation of porous RNA nanospheres and their application in synergistic targeted therapeutics of hepatocellular carcinoma
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环糊精介导的多孔RNA纳米球的形成及其在肝细胞癌协同靶向治疗中的应用
DOI：
10.1016/j.biomaterials.2020.120304
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发表时间：
2020-12-01
期刊：
影响因子：
14
通讯作者：
Li, Jinjun
中科院分区：
文献类型：
--
作者：
Chen, Xiaoxia;Chen, Tianshu;Li, Jinjun
球形和多孔性纳米颗粒是理想的药物输送纳米结构。但目前它们主要由不可降解的无机材料组成，阻碍了其临床应用。在这里，以RNA为构建块，以环糊精为粘合剂，合成了生物多孔纳米球。该RNA含有用于靶向递送EpCAM的适体和用于基因沉默的siRNA，而环糊精可通过其疏水空腔装载肝癌靶向治疗的核心药物不溶性索拉非尼。在适配子的辅助下，多孔纳米球被靶向肝癌细胞内化后，可以被细胞质的Dird酶降解，释放siRNA和索拉非尼进行协同治疗。多孔RNA纳米球的协同作用已在体外功能测试、皮下荷瘤小鼠和体内原位荷瘤小鼠模型中得到验证。鉴于基因治疗与化疗协同的广阔前景，以及多孔纳米球的RNA和环糊精可以分别负载各种类型的siRNA和小分子药物的事实，这种形式的生物多孔纳米球为靶向输送适合治疗特定肿瘤的药物提供了机会。
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.