Department of Hepatobiliary Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014, People's Republic of China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
Drug Deliv Transl Res. 2023 Mar;13(3):782-794. doi: 10.1007/s13346-022-01237-z. Epub 2022 Sep 16.
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.
环状 RNA(circRNAs)是一类高度稳定的闭环非编码 RNA,参与肝癌(HCC)的发生和发展。然而,环状 RNA 在 HCC 中的治疗作用知之甚少。我们发现高表达 circ_0058051 与 HCC 患者的预后呈负相关。circ_0058051 敲低可减弱 HCC 细胞的增殖和集落形成能力,同时抑制迁移。circ_0058051 可能被用作 HCC 基因治疗的靶点。我们基于超顺磁性氧化铁纳米颗粒(SPIONs)合成了一种新型小干扰 RNA(siRNA)递药系统,PEG-PCL-PEI-C14-SPIONs(PPPCSs)。PPPCSs 可保护 circ_0058051 的 siRNA 免受血清中降解,并将 siRNA 有效递送至 SMMC-7721 细胞。同时,静脉注射 PPPCSs/siRNA 复合物可抑制皮下肿瘤模型中的肿瘤生长。此外,该纳米复合物对裸鼠的器官无毒性。上述结果表明,PPPCSs/si-circ_0058051 复合物可能为 HCC 治疗提供一种新的有前途的方法。