Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2022-09-16 , DOI: 10.1007/s13346-022-01237-z Song You 1, 2, 3 , Zijin Luo 2 , Niangmei Cheng 2, 4 , Ming Wu 2, 4 , Yongping Lai 2 , Fei Wang 2 , Xiaoyuan Zheng 2 , Yingchao Wang 2, 4 , Xiaolong Liu 2, 4 , Jingfeng Liu 1, 2, 4 , Bixing Zhao 2, 4
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Circular RNAs (circRNAs) are a class of highly stable and closed-loop noncoding RNA that are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 knockdown attenuated the proliferation and colony formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system, PEG-PCL-PEI-C14-SPIONs (PPPCSs), based on superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected the siRNA of circ_0058051 from degradation in serum and effectively delivered siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment.
Graphical abstract
中文翻译：
靶向circRNA circ_0058051的磁响应纳米平台抑制肝细胞癌进展
环状RNA（circRNA）是一类高度稳定的闭环非编码RNA，参与肝细胞癌（HCC）的发生发展。然而，人们对 circRNA 在 HCC 中的治疗作用知之甚少。我们发现circ_0058051的高表达与HCC患者的预后呈负相关。Circ_0058051 敲低减弱了增殖和集落形成，同时抑制了 HCC 细胞的迁移。Circ_0058051 可用作 HCC 基因治疗的靶标。我们基于超顺磁性氧化铁纳米粒子 (SPION) 合成了一种新型小干扰 RNA (siRNA) 递送系统 PEG-PCL-PEI-C14-SPION (PPPCS)。PPPCSs 保护 circ_0058051 的 siRNA 在血清中不被降解，并将 siRNA 有效地递送到 SMMC-7721 细胞中。同时，静脉注射 PPPCSs/siRNA 复合物可以抑制皮下肿瘤模型中的肿瘤生长。此外，该纳米复合材料对裸鼠器官无毒性。上述结果表明，PPPCSs/si-circ_0058051复合物可能提供一种新颖且有前景的HCC治疗方法。
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